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Lu B, Dvorani E, Nguyen L, Beca JM, Mercer RE, Adamic A, Muñoz C, Chan KKW. Cost-Effectiveness Analysis of Bevacizumab Biosimilars Versus Originator Bevacizumab for Metastatic Colorectal Cancer: A Comparative Study Using Real-World Data. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2024; 27:1689-1697. [PMID: 39127249 DOI: 10.1016/j.jval.2024.07.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 06/10/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024]
Abstract
OBJECTIVES MVASI (Amgen) and Zirabev (Pfizer) are 2 of the earliest bevacizumab biosimilars approved for the first-line treatment of metastatic colorectal cancer (mCRC). We aimed to confirm and quantify the real-world cost savings and cost-effectiveness of MVASI and Zirabev relative to originator bevacizumab for patients with mCRC. METHODS We conducted a population-based, retrospective cohort study in Ontario, Canada, where originator and biosimilar bevacizumab are universally publicly funded. All mCRC patients who received originator bevacizumab between January 2008 and August 2019 or biosimilar bevacizumab between August 2019 and March 2021 were propensity score matched (1:4) to adjust for baseline differences. Total 1-year patient-level costs (CAD) and effects (life years [LY] and quality-adjusted LYs) were calculated from the public health payer's perspective. Primary outcomes included incremental net monetary benefit and incremental net health benefit (INHB). Sensitivity analyses included a subgroup analysis by biosimilar type (MVASI/Zirabev) and a 2-year analysis. RESULTS The matched cohort included 747 biosimilar cases and 2945 comparators. Bevacizumab biosimilars were associated with an incremental cost of -$6379 (95%CI: -9417, -3537) (ie, cost saving) and incremental effect of 0.0 (95% CI: -0.02, 0.02) LY and -0.01 (95% CI: -0.03, 0) quality-adjusted LYs gained. Incremental net monetary benefit and INHB estimates were $6331 (95% CI: 6245, 6417) and 0.127 LY (95% CI: 0.125, 0.128), respectively, at a willingness-to-pay threshold of $50 000/life year gained, with all estimates indicating the cost-effectiveness of biosimilar bevacizumab. Cost-effectiveness remained consistent across biosimilar brand subgroups and 2-year sensitivity analyses. CONCLUSION Bevacizumab biosimilars demonstrated real-world cost savings while providing similar survival benefit as originator bevacizumab, confirming the initial expectations of their implementation and supporting health system sustainability.
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Affiliation(s)
- Brandon Lu
- Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | | | - Jaclyn M Beca
- Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada; Morse Consulting Inc., Toronto, ON, Canada
| | - Rebecca E Mercer
- Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada; Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
| | - Andrea Adamic
- Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada; Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
| | - Caroline Muñoz
- Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada; Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
| | - Kelvin K W Chan
- Sunnybrook Health Sciences Centre, Toronto, ON, Canada; ICES, Toronto, ON, Canada; Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada; Morse Consulting Inc., Toronto, ON, Canada.
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Barcina Lacosta T, Inotai A, Pereira CL, Barbier L, Simoens S. Mapping Health Technology Assessment Agency Approaches for Biosimilar Value Assessment: An ISPOR Special Interest Group Report. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2024; 27:543-551. [PMID: 38702140 DOI: 10.1016/j.jval.2024.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 01/28/2024] [Accepted: 01/31/2024] [Indexed: 05/06/2024]
Abstract
OBJECTIVES A systematic literature review undertaken by the ISPOR Biosimilar Special Interest Group highlighted that limited guidance exists on how to assess biosimilars value and on appropriate economic evaluation techniques. This study described current health technology assessment (HTA) agency approaches for biosimilar value assessment. METHODS Semi-structured interviews (n = 16) were carried out with HTA experts in Africa, America, Asia, Australia, and Europe to investigate current HTA practices for biosimilars. Data categorization was based on a thematic analysis approach. Findings from the qualitative data analysis were interpreted in view of relevant published literature. RESULTS Our research suggests that in systems in which frameworks for biosimilar regulatory approval are well established, HTA agencies can accept the regulators' comparability exercise, and reimbursement decisions can generally be based on price comparisons. This approach is accepted in practice and allows streamlining of biosimilars value assessment. Nevertheless, conducting HTAs for biosimilars can be relevant when (1) the originator is not reimbursed, (2) the biosimilar marketing authorization holder seeks reimbursement for indications/populations, pharmaceutical forms, methods and routes of administration that differ with respect to the originator, and (3) a price premium is sought for a biosimilar based on an added-value claim. Further, HTA agencies' role conducting class-review updates following biosimilar availability can support greater patients' access to biologics. CONCLUSIONS Internationally, there are differences in how national competent authorities on pricing and reimbursement of pharmaceuticals perceive HTA's role for biosimilars. Therefore, HTA agencies are encouraged to issue clear guidance on when and how to conduct HTAs for biosimilars, and on which economic techniques to apply.
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Affiliation(s)
| | - András Inotai
- Center for Health Technology Assessment, Semmelweis University, Budapest, Hungary; Syreon Research Institute, Budapest, Hungary
| | | | - Liese Barbier
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Steven Simoens
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
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Moorkens E, Lacosta TB, Dawoud D, Inotai A, Janodia M, Tan CJ, Lim KK, Khatri N, Pereira CL, Simoens S. A Systematic Literature Review of Gaps and Challenges in Value Assessment of Biosimilars: An ISPOR Special Interest Group Report. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2023; 26:1137-1144. [PMID: 37516531 DOI: 10.1016/j.jval.2023.04.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 03/22/2023] [Accepted: 04/10/2023] [Indexed: 07/31/2023]
Abstract
OBJECTIVES This study aims to provide an overview of the gaps and challenges in the value assessment of biosimilars and to identify potential approaches to address them. METHODS A multidisciplinary, international team of biosimilar experts identified gaps and challenges. A systematic review was conducted of the peer-reviewed literature in PubMed, EMBASE, Web of Science Core Collection, EBSCOhost Business Source Complete; and of the gray literature. Preliminary results were presented at ISPOR conferences and this article benefited from 2 review rounds among ISPOR Biosimilar Special Interest Group members. RESULTS Given that a biosimilar is highly similar to its reference biologic, health technology assessment agencies should accept the comparability exercise approved by regulatory authorities and, thus, conduct a price comparison when biosimilar reimbursement is requested for the same indication as the reference biologic. If the reference biologic is not reimbursed or is not the standard of care, a full economic evaluation of the biosimilar versus a relevant comparator needs to be conducted. To date, little consideration has been given to specific challenges, such as how biosimilar value assessment can account for the nocebo effect, potential differences between biologic-naive and biologic-experienced patients, the availability of intravenous and subcutaneous administration forms or different administration devices for the same active compound, value-added services, and the contribution of biosimilars for generating health gain at the population level. CONCLUSIONS There is a need to gather further insights in the methodology of value assessment for biosimilars, and health technology assessment agencies need to develop more elaborate guidance on biosimilar value assessment in specific circumstances.
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Affiliation(s)
- Evelien Moorkens
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | | | - Dalia Dawoud
- National Institute for Health and Care Excellence (NICE), London, England, UK; Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - András Inotai
- Center for Health Technology Assessment, Semmelweis University, Budapest, Hungary; Syreon Research Institute, Budapest, Hungary
| | - Manthan Janodia
- Department of Pharmacy Management, Manipal College of Pharmaceutical Sciences, Manipal, India
| | - Chia Jie Tan
- Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA
| | - Ka Keat Lim
- School of Population Health & Environmental Sciences, Faculty of Life Sciences & Medicine, King's College London, London, England, UK; Biomedical Research Centre, National Institute for Health Research (NIHR), Guy's and St Thomas' NHS Foundation Trust and King's College London, London, England, UK
| | - Nishtha Khatri
- Department of Pharmacology & Therapeutics, Seth GS Medical College and KEM Hospital, Mumbai, India
| | | | - Steven Simoens
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
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Ulu K, Çakan M, Çağlayan Ş, Yiğit RE, Demir F, Coşkuner T, Kardeş E, Sözeri B. Real-life data on efficacy and safety of original Adalimumab and biosimilar Adalimumab (ABP 501) in pediatric rheumatic diseases. Expert Opin Biol Ther 2023; 23:833-839. [PMID: 36101926 DOI: 10.1080/14712598.2022.2123703] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 09/08/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND We aimed to compare the efficacy and safety of the original product (OP) and biosimilar product (BP) of adalimumab in pediatric rheumatic diseases. RESEARCH DESIGN AND METHODS The study group consisted of patients who had received original or biosimilar adalimumab (ABP 501) therapy for at least 3 months. The patients were divided into uveitis and arthritis groups based on the indication of adalimumab treatment. Assessment of disease activity was performed by Juvenile Arthritis Disease Activity Score in patients with juvenile idiopathic arthritis, and by standardization of uveitis nomenclature criteria in patients with uveitis. RESULTS The study included 140 patients, of which 87 were treated with OP and 53 with BP. In the arthritis group, 26 (63.4%) and 20 (57.1%) patients reached inactive disease according to JADAS-27 in the original and biosimilar adalimumab groups, respectively. In the uveitis group the mean number of exacerbations throughout the treatment period was 0.84 ± 1.07 in the OP group, and 0.58 ± 0.79 in the BP group. There were 71 treatment-emergent adverse events in the OP group and 38 in the BP group. CONCLUSION There was no significant difference between the biosimilar and the original product in efficacy and safety.
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Affiliation(s)
- Kadir Ulu
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
| | - Mustafa Çakan
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
| | - Şengül Çağlayan
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
| | - Ramazan Emre Yiğit
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
| | - Ferhat Demir
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
| | - Taner Coşkuner
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
| | - Esra Kardeş
- Department of Ophthalmology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
| | - Betül Sözeri
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, Istanbul, Turkey
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Ismail S, Abu Esba L, Khan M, Al-Abdulkarim H, Modimagh H, Yousef C. An Institutional Guide for Formulary Decisions of Biosimilars. Hosp Pharm 2023; 58:38-48. [PMID: 36644755 PMCID: PMC9837324 DOI: 10.1177/00185787221138007] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Biologics have changed the landscape for the management of many debilitating chronic diseases but account for a significant expenditure of medications globally. Fortunately, advances in technology paved the way for the introduction of biosimilars, which are highly similar to the originator biologics. In the quest to reduce the budget impact of biologics, organizations have begun to adopt biosimilars. Institutions evaluating biosimilars for inclusion in the hospital formulary must make informed formulary decisions by conducting a thorough review of key elements for evaluation of biosimilars and address the multidimensional aspects during the selection process of different biosimilar products. Therefore, we aim to present an institutional guide of these elements to inform formulary decisions. These key elements include biosimilar evaluation for formulary addition; regulatory approval; substitution, interchangeability, and switching; extrapolation; product characteristics, manufacturing, and supply chain issues; pharmacoeconomic evaluations; traceability, nomenclature, and coding; education; and pharmacovigilance.
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Affiliation(s)
- Sherin Ismail
- Pharmaceutical Care Department, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
- University of North Carolina, Chapel Hill, NC, USA
| | - Laila Abu Esba
- King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
- College of pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Pharmaceutical Care Department, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Mansoor Khan
- Pharmaceutical Care Department, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
| | - Hana Al-Abdulkarim
- King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
- Doctoral School of Applied Informatics and Applied Mathematics, Óbuda University, Budapest, Hungary
- Drug Policy and Economic Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Hind Modimagh
- King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
- College of pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Pharmaceutical Care Department, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Consuela Yousef
- King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
- Pharmaceutical Care Department, Ministry of National Guard Affairs, Dammam, Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Al Ahsa, Saudi Arabia
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Najeeb H, Yasmin F, Surani S. Emerging role of biosimilars in the clinical care of inflammatory bowel disease patients. World J Clin Cases 2022; 10:4327-4333. [PMID: 35663066 PMCID: PMC9125297 DOI: 10.12998/wjcc.v10.i14.4327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/20/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
The increasing incidence of inflammatory bowel disease (IBD) globally has redirected the healthcare system's focus towards safe and affordable pharmacological interventions. The inception of anti-tumor necrosis factor-α (TNF-α) had resulted in a trend shift from surgical interventions. However, as the patents of approved anti-TNF-α drugs expire, biological copies of the many approved products are in the pipeline. The most commonly used biosimilar for IBD has been infliximab, followed by Adalimumab biosimilars which have been approved in major countries across the world. Although biosimilars are approved on the basis of similarity of their reference product, the lack of real-world evidence of its safety in ulcerative colitis and Crohn's disease patients has contributed to physicians' hesitancy. However, biosimilars are expected to reduce treatment costs and provide economic benefits.
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Affiliation(s)
- Hala Najeeb
- Department of Internal Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Farah Yasmin
- Department of Internal Medicine, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Salim Surani
- Department of Medicine, Texas A&M University, College Station, TX 77843, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States
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Wong G, Wang K, Pasetka M, Zhang L, Lou J, Majeed H, Flores J, Lam E, DeAngelis C. The Real-World Experience of the Biosimilar (Grastofil®) to the Reference Biologic (Neupogen®) in Breast Cancer and Lymphoma: A Canadian Single-Centre Retrospective Study. Curr Oncol 2022; 29:1349-1369. [PMID: 35323315 PMCID: PMC8947031 DOI: 10.3390/curroncol29030115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/18/2022] [Accepted: 02/20/2022] [Indexed: 12/04/2022] Open
Abstract
Febrile neutropenia (FN) is a common side effect of cytotoxic chemotherapy that may result in poor treatment outcomes. The short acting granulocyte colony stimulating factors (G-CSF) act to stimulate granulocytes to increase production of white blood cells. The filgrastim biosimilar is useful, as it may provide a cheaper and equally effective treatment to FN. This study explored the usage of the filgrastim biosimilar (Grastofil®) and the reference biologic (Neupogen®) in breast cancer and lymphoma patients. A retrospective chart review of patients receiving Grastofil® from January 2017 to June 2019 or Neupogen® for primary prophylaxis of FN from January 2013 to December 2017 was conducted. The endpoints included the incidence of FN and the occurrence of dose reduction (DR) and dose delay (DD). One hundred and fifty-three Grastofil® patients were matched to 153 Neupogen® patients. This cohort was further split into breast cancer (n = 275) and non-Hodgkin’s lymphoma (n = 31) cohorts. After adjusting for chemotherapy cycles, the biosimilar filgrastim was non-inferior to the reference biologic based on FN incidence in addition to related outcomes including DR and DD.
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Affiliation(s)
- Gina Wong
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (K.W.); (M.P.); (H.M.); (E.L.); (C.D.)
- Correspondence:
| | - Katie Wang
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (K.W.); (M.P.); (H.M.); (E.L.); (C.D.)
| | - Mark Pasetka
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (K.W.); (M.P.); (H.M.); (E.L.); (C.D.)
| | - Liying Zhang
- Macrostat Inc., Toronto, ON L4B 4P4, Canada; (L.Z.); (J.L.)
| | - Julia Lou
- Macrostat Inc., Toronto, ON L4B 4P4, Canada; (L.Z.); (J.L.)
| | - Habeeb Majeed
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (K.W.); (M.P.); (H.M.); (E.L.); (C.D.)
| | - Jerome Flores
- Department of Pharmacy, University Health Network, University of Toronto, Toronto, ON M5G 2C4, Canada;
| | - Emily Lam
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (K.W.); (M.P.); (H.M.); (E.L.); (C.D.)
| | - Carlo DeAngelis
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada; (K.W.); (M.P.); (H.M.); (E.L.); (C.D.)
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Chisari CG, Sgarlata E, Arena S, Toscano S, Luca M, Patti F. Rituximab for the treatment of multiple sclerosis: a review. J Neurol 2022; 269:159-183. [PMID: 33416999 PMCID: PMC7790722 DOI: 10.1007/s00415-020-10362-z] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 12/03/2020] [Accepted: 12/08/2020] [Indexed: 01/07/2023]
Abstract
In the last decades, evidence suggesting the direct or indirect involvement of B cells on multiple sclerosis (MS) pathogenesis has accumulated. The increased amount of data on the efficacy and safety of B-cell-depleting therapies from several studies has suggested the addition of these drugs as treatment options to the current armamentarium of disease modifying therapies (DMTs) for MS. Particularly, rituximab (RTX), a chimeric monoclonal antibody directed at CD20 positive B lymphocytes resulting in cell-mediated apoptosis, has been demonstrated to reduce inflammatory activity, incidence of relapses and new brain lesions on magnetic resonance imaging (MRI) in patients with relapsing-remitting MS (RRMS). Additional evidence also demonstrated that patients with progressive MS (PMS) may benefit from RTX, which also showed to be well tolerated, with acceptable safety risks and favorable cost-effectiveness profile.Despite these encouraging results, RTX is currently approved for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, several forms of vasculitis and rheumatoid arthritis, while it can only be administered off-label for MS treatment. Between Northern European countries exist different rules for using not licensed drug for treating MS. The Sweden MS register reports a high rate (53.5%) of off-label RTX prescriptions in relation to other annually started DMTs to treat MS patients, while Danish and Norwegian neurologists have to use other anti-CD20 drugs, as ocrelizumab, in most of the cases.In this paper, we review the pharmacokinetics, pharmacodynamics, clinical efficacy, safety profile and cost effectiveness aspects of RTX for the treatment of MS. Particularly, with the approval of new anti-CD20 DMTs, the recent worldwide COVID-19 emergency and the possible increased risk of infection with this class of drugs, this review sheds light on the use of RTX as an alternative treatment option for MS management, while commenting the gaps of knowledge regarding this drug.
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Affiliation(s)
- Clara Grazia Chisari
- Department "GF Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy
| | - Eleonora Sgarlata
- Department "GF Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy
- Stroke Unit, Department of Medicine, Umberto I Hospital, Siracusa, Italy
| | - Sebastiano Arena
- Department "GF Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy
| | - Simona Toscano
- Department "GF Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy
| | - Maria Luca
- Department "GF Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy
| | - Francesco Patti
- Department "GF Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy.
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Demirkan FG, Ulu K, Öztürk K, Karadağ ŞG, Özdel S, Sönmez HE, Çakmak F, Demir F, Sözeri B, Aktay Ayaz N. Toward the integration of biosimilars into pediatric rheumatology: adalimumab ABP 501 experience of PeRA research group. Expert Opin Biol Ther 2021; 22:197-202. [PMID: 34730483 DOI: 10.1080/14712598.2021.2002296] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To review the real-life data, to provide an input to the literature concerning treatment of juvenile idiopathic arthritis (JIA) with adalimumab (ADL) biosimilar. METHOD This multi-centric retrospective study was conducted among children with JIA, followed up for at least 24-weeks from the initiation of ADL biosimilar (ABP 501) treatment. Adverse events and alterations in disease activity scores were figured out. RESULTS The median age of the group was 15.5 (5-18) years. JIA categories were oligoarticular (n =12), enthesitis-related (ERA) (n=24), psoriatic (PsA) (n=6), and polyarticular (n=4). Uveitis was detected at the initiation of the disease (n=3), during the disease course (n=5), or before the diagnosis (n=1). The first-line treatment preferences were ADL biosimilar (n=37) and etanercept (n=9). On the 6th month of ABP 501, 40 (86.9%) patients had achieved complete remission. Six patients (1 PsA, 1 polyarticular JIA, and 4 ERA) had ongoing active arthritis. Furthermore, all except one of the patients had remission of ophthalmologic findings. No life-threatening adverse events were observed. CONCLUSIONS ABP 501 has a gradual increase in prescription in pediatric rheumatology. Real-life data of the cohort announce that ADL biosimilar is a suitable and effective treatment option for patients with JIA in case of indication.
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Affiliation(s)
- Fatma Gül Demirkan
- Department of Pediatric Rheumatology, Istanbul University, Istanbul School of Medicine, İstanbul, Turkey
| | - Kadir Ulu
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Research and Training Hospital, Istanbul, Turkey
| | - Kübra Öztürk
- Department of Pediatric Rheumatology, Istanbul Medeniyet University, School of Medicine, Goztepe Research and Training Hospital, Istanbul, Turkey
| | - Şerife Gül Karadağ
- Department of Pediatric Rheumatology, University of Health Sciences, Bakırköy Dr. SadiKonuk Training and Research Hospital, İstanbul, Turkey
| | - Semanur Özdel
- Department of Pediatric Rheumatology, University of Health Sciences, Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Ankara, Turkey
| | - Hafize Emine Sönmez
- Department of Pediatric Rheumatology, Kocaeli University, Kocaeli School of Medicine, Kocaeli, Turkey
| | - Figen Çakmak
- Department of Pediatric Rheumatology, Istanbul University, Istanbul School of Medicine, İstanbul, Turkey
| | - Ferhat Demir
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Research and Training Hospital, Istanbul, Turkey
| | - Betül Sözeri
- Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Research and Training Hospital, Istanbul, Turkey
| | - Nuray Aktay Ayaz
- Department of Pediatric Rheumatology, Istanbul University, Istanbul School of Medicine, İstanbul, Turkey
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Barberio B, Cingolani L, Canova C, Barbieri G, Sablich R, Urbano MT, Bertani L, Costa F, Bodini G, Demarzo MG, Ferronato A, Buda A, Melatti P, Massimi D, Savarino EV, Zingone F. A propensity score-weighted comparison between adalimumab originator and its biosimilars, ABP501 and SB5, in inflammatory bowel disease: a multicenter Italian study. Therap Adv Gastroenterol 2021; 14:17562848211031420. [PMID: 34349836 PMCID: PMC8295962 DOI: 10.1177/17562848211031420] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 06/22/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Adalimumab is an effective and safe biological drug for the treatment of inflammatory bowel disease (IBD). Nowadays, several biosimilar agents are available, but data regarding their efficacy and safety in patients with IBD are still lacking. We aimed to compare the effectiveness and tolerability between adalimumab originator, ABP501 and SB5 biosimilars in patients with IBD in the short term (after induction and after 6 months of treatment) through a propensity score-weighted multicenter cohort study. METHODS We included 156 patients with IBD, 69 patients with ulcerative colitis and 87 patients with Crohn's disease (CD) receiving ABP501 or SB5 biosimilars from January 2019 to April 2020 for moderate-to-severe disease. For comparison, a group of age- and sex-matched patients treated with adalimumab originator was used. We collected clinical and biochemical data after induction and at 6 months of treatment. Endoscopic data were recorded only at baseline. RESULTS Overall, clinical benefit was achieved by 86.4% and 85.3% after induction and at 6 months, respectively, without a statistically significant difference between the three treatment groups (p = 0.68 and p = 0.46). However, after induction, we found significant differences between the two types of the disease (ulcerative colitis or CD, p = 0.004), with a greater clinical benefit achieved by patients with CD. Also, the therapeutic optimization rate between the three drugs was not statistically significant different (p = 0.30). All treatments showed a good safety profile, with only 10 patients who needed to stop therapy because of adverse events. CONCLUSION Adalimumab biosimilars seem to be as effective and safe as the originator in patients with IBD. Surely, they represent a great opportunity to reduce the costs of biological therapies, however larger and longer real-life studies are necessary.
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Affiliation(s)
| | | | - Cristina Canova
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Giulia Barbieri
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Renato Sablich
- Gastroenterology Unit, Santa Maria degli Angeli Hospital, Pordenone, Friuli-Venezia Giulia, Italy
| | - Maria Teresa Urbano
- Gastroenterology Unit, Santa Maria degli Angeli Hospital, Pordenone, Friuli-Venezia Giulia, Italy
| | - Lorenzo Bertani
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Francesco Costa
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Maria Giulia Demarzo
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Antonio Ferronato
- Endoscopy Unit, Alto Vicentino Hospital, AULSS7 Pedemontana, Santorso, Veneto, Italy
| | - Andrea Buda
- Gastroenterology Unit, Hospital Feltre, Italy
| | - Piera Melatti
- Department of Surgery, Oncology, Gastroenterology, University of Padua, Padua, Veneto, Italy
| | - Davide Massimi
- Department of Surgery, Oncology, Gastroenterology, University of Padua, Padua, Veneto, Italy
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11
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Barszczewska O, Piechota A. The Impact of Introducing Successive Biosimilars on Changes in Prices of Adalimumab, Infliximab, and Trastuzumab-Polish Experiences. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18136952. [PMID: 34209612 PMCID: PMC8297232 DOI: 10.3390/ijerph18136952] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/16/2021] [Accepted: 06/24/2021] [Indexed: 11/16/2022]
Abstract
Biosimilars are cheaper than original drugs and are thus of interest to the public. The aim of this article is to assess the benefits of introducing more than one biosimilar for the same substance (active pharmaceutical ingredient, API). The hypothesis is that the introduction of successive biosimilars of a specific original drug reduces the price of the selected API. The study focuses on drug prices varying with the successive arrival of new biosimilars. Three drugs that have at least three reimbursed biosimilars on the market were selected, two from the same therapeutic group (adalimumab and infliximab) and one (trastuzumab) representing another class of drugs. The following data were analyzed: price variation after the introduction of the first, second, and third biosimilar, and the average price reduction for all three biosimilars. Additionally, a literature review was conducted. The reimbursement of each new biosimilar is beneficial since it is associated with a price reduction in percentage terms. However, the first biosimilar brought about the greatest savings due to the higher initial prices of the original drugs and to Polish reimbursement rules. This article is helpful for when taking healthcare decisions regarding the pricing of and reimbursement for new biosimilars.
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Affiliation(s)
- Olga Barszczewska
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-131 Lodz, Poland
- Correspondence: ; Tel.: +48-692-508-605
| | - Anna Piechota
- Department of Insurance, University of Lodz, 90-001 Lodz, Poland;
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12
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Santos-Neto JF, Oliveira FO, Hodel KVS, Fonseca LMS, Badaró R, Machado BAS. Technological Advancements in Monoclonal Antibodies. ScientificWorldJournal 2021; 2021:6663708. [PMID: 33628140 PMCID: PMC7892242 DOI: 10.1155/2021/6663708] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 01/11/2021] [Accepted: 01/21/2021] [Indexed: 12/20/2022] Open
Abstract
Biopharmaceuticals are innovative solutions that have revolutionized the treatment of important chronic diseases and malignancies. The approval of biosimilar products has become a complex and balanced process, and there are versions of drugs with established biosimilarity that can offer a more accessible treatment option to patients. The objective of this work was to identify the advancement of these technologies by means of patent and article analysis based on technological and scientific prospection. In patent document recovery, Derwent Innovation Index (DWPI) and PatentInspiration databases were used. The research was based on the search of the selected terms in the title, summary, and claims of the documents through a search strategy containing IPC code and keywords. In articles recovery, the Web of Science tool was used in the search of scientific publications dated from the last 5 years. The search resulted in a total of 2295 individual patent documents and 467 families using DWPI database, 769 individual patents and 205 families using PatentInspiration, and 2602 articles using Web of Science database. Additionally, this work describes the number of organizations that contribute to this area, where they are, how much development they have undergone, and the inventors/authors involved. Based on the number of publications registered, there is an important prominence for scientific research in mAbs. In terms of innovation, it is expected that several therapeutic drugs are already under regulatory review, which will allow drugs to be approved over the next few years and will thus generate a continuous flow of new products based on immunotherapies, mAbs, and biosimilar drugs. These drugs have become essential weapons for the treatment of significant diseases, and the increasing trend in the number of related scientific and technological publications contributes to making these therapies available to the greatest number of people.
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Affiliation(s)
- José F. Santos-Neto
- University Center SENAI/CIMATEC, National Service of Industrial Learning–SENAI, Salvador, Bahia, Brazil
| | - Fabricia O. Oliveira
- SENAI Institute of Innovation (ISI) in Advanced Health Systems (CIMATEC ISI SAS), University Center SENAI/CIMATEC, National Service of Industrial Learning–SENAI, Salvador, Bahia, Brazil
| | - Katharine V. S. Hodel
- SENAI Institute of Innovation (ISI) in Advanced Health Systems (CIMATEC ISI SAS), University Center SENAI/CIMATEC, National Service of Industrial Learning–SENAI, Salvador, Bahia, Brazil
| | - Larissa M. S. Fonseca
- SENAI Institute of Innovation (ISI) in Advanced Health Systems (CIMATEC ISI SAS), University Center SENAI/CIMATEC, National Service of Industrial Learning–SENAI, Salvador, Bahia, Brazil
| | - Roberto Badaró
- SENAI Institute of Innovation (ISI) in Advanced Health Systems (CIMATEC ISI SAS), University Center SENAI/CIMATEC, National Service of Industrial Learning–SENAI, Salvador, Bahia, Brazil
| | - Bruna A. S. Machado
- University Center SENAI/CIMATEC, National Service of Industrial Learning–SENAI, Salvador, Bahia, Brazil
- SENAI Institute of Innovation (ISI) in Advanced Health Systems (CIMATEC ISI SAS), University Center SENAI/CIMATEC, National Service of Industrial Learning–SENAI, Salvador, Bahia, Brazil
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Dutta B, Huys I, Vulto AG, Simoens S. Identifying Key Benefits in European Off-Patent Biologics and Biosimilar Markets: It is Not Only About Price! BioDrugs 2021; 34:159-170. [PMID: 31792843 PMCID: PMC7113204 DOI: 10.1007/s40259-019-00395-w] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other patient groups, or that the biologic therapy can be moved to an earlier line of treatment. Cost savings from biosimilars can be used to increase patient access to therapy or to increase the number of healthcare professionals. Finally, competition between off-patent biologics and biosimilars may stimulate an innovation in the formulation and development of next-generation biologics. Our paper illustrates that the benefit of off-patent biologics and biosimilars is not restricted to cost savings, but that these medicines may contribute to an expansion of medical treatment options for patients, hence concomitantly contributing to the long-term sustainability of the healthcare system. This review provides a broader view for clinical and economic decision makers and healthcare professionals on the added benefits of off-patent biologics and their use in clinical practice.
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Affiliation(s)
- Binita Dutta
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Louvain, Belgium
| | - Isabelle Huys
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Louvain, Belgium
| | - Arnold G Vulto
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Louvain, Belgium. .,Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
| | - Steven Simoens
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Louvain, Belgium
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14
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Wong G, Zhang L, Majeed H, Razvi Y, DeAngelis C, Lam E, McKenzie E, Wang K, Pasetka M. A retrospective review of the real-world experience of the Pegfilgrastim biosimilar (Lapelga®) to the reference biologic (Neulasta®). J Oncol Pharm Pract 2020; 28:5-16. [PMID: 33215563 PMCID: PMC8669212 DOI: 10.1177/1078155220974085] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Introduction Cancer patients receiving myelosuppressive chemotherapy are vulnerable to febrile neutropenia (FN) which contributes to poor treatment outcomes. The use of granulocyte colony-stimulating factors is administered to prevent chemotherapy-induced neutropenia. The introduction of biosimilars has allowed for greater cost-savings while maintaining safety and efficacy. This retrospective study assessed the incidence of FN and related treatment outcomes and the cost minimization of a pegfilgrastim biosimilar and its reference. Methods A retrospective chart review of breast cancer patients receiving (neo) adjuvant chemotherapy from February 2017 to May 2020 was conducted. The endpoints included the incidence of FN, the occurrence of dose reduction (DR), dose delay (DD) and pain. A cost minimization analysis was performed from a third-party payer perspective. Results One hundred Neulasta® and 74 Lapelga® patients were included in the first-cycle analysis. The rate of FN in cycle 1 for Neulasta® and Lapelga® was 2/100 and 4/74, respectively; risk difference (RD) = 3.4%; 95% CI: –2.4 to 9.2%. Eighty-three Neulasta® and 59 Lapelga® patients were included in the all-cycle analyses, where DR was reported in 76 (15%) Neulasta® cycles vs 33 (10%) Lapelga® cycles (RD = –3.6, 95% CI: –10.2 to 2.9). DD was reported in 20 (4%) Neulasta® cycles vs. 11 (3.5%) Lapelga® cycles (RD = –0.3; 95% CI: –2.7 to 2.0). Adverse events were similar between groups. Cost minimization using a cohort of 20,000 patients translated into an incremental savings of $21,606,800 CAD for each cycle. Conclusion The biosimilar pegfilgrastim was non-inferior to the reference biologic based on FN incidence in addition to related outcomes including DR and DD.
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Affiliation(s)
- Gina Wong
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Liying Zhang
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Habeeb Majeed
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Yasmeen Razvi
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Carlo DeAngelis
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Emily Lam
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Erin McKenzie
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Katie Wang
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Mark Pasetka
- Odette Cancer Centre, 71545Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
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15
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Huang HY, Liu CC, Yu Y, Wang L, Wu DW, Guo LW, Wang SH, Fang H, Bai Y, Fang Y, Fan Q, Sun C, Wu Y, Shi JF, Ma F, Tang Y, Dai M, Li N. Pharmacoeconomic Evaluation of Cancer Biosimilars Worldwide: A Systematic Review. Front Pharmacol 2020; 11:572569. [PMID: 33536905 PMCID: PMC7849203 DOI: 10.3389/fphar.2020.572569] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 10/06/2020] [Indexed: 12/21/2022] Open
Abstract
Background and Purpose: The availability of oncology biosimilars is deemed as a fundamental strategy to achieve sustainable health care. However, there is scarce systematic evidence on economic effectiveness of cancer biosimilars. We aimed to synthesize evidence from pharmacoeconomic evaluation of oncology biosimilars globally, provide essential data and methodological reference for involved stakeholders. Materials and Methods: This systematic review was conducted in PubMed, embase, the Cochrane library, CRD, ISPOR and NICE utill December 31, 2019. Information on basic characteristics, evaluation methodology and results were extracted. Quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards Checklist. Results: For 17 studies identified (13 from Europe and four from United States), the overall quality was generally acceptable. A total of seven biological molecules involved with filgrastim, EPOETIN α, and trastuzumab leading the three. The mostly common evaluation perspective was payer, but the time horizon varied greatly. There were ten studies which adopted cost minimization analysis to evaluate efficiency while seven studies adopted budget impact analysis to address affordability, with cost ratio and cost saving being its corresponding primary endpoint. Although the comparability of included studies was limited and specific results were largely affected by uptake and price discount rates of the oncology biosimilar, the comprehensive results consistently favored its promotion. Conclusion: Globally, the economic evaluation of cancer biosimilars is in its initial phase. However, limited evidence from developed countries consistently supported both cost-effectiveness of efficiency and affordability of oncology biosimilars, while they were largely affected by uptake and price discount rate.
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Affiliation(s)
- Hui-Yao Huang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Cheng-Cheng Liu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Yu
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Le Wang
- Institute of Cancer and Basic Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
| | - Da-Wei Wu
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lan-Wei Guo
- Office for Cancer Control and Research, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China
| | - Shu-Hang Wang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Fang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ying Bai
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Fang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qi Fan
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chao Sun
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ying Wu
- Pfizer Investment Co., Ltd., Shanghai, China
| | - Ju-Fang Shi
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Tang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min Dai
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Li
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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16
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Shakeel S, Hassali MA, Rehman H, Rehman AU, Muneswarao J. Knowledge, Attitude, and Practice Towards Biosimilars and Interchangeable Products: A Prescriptive Insight by the Pharmacists. Int J Gen Med 2020; 13:1075-1082. [PMID: 33204142 PMCID: PMC7667000 DOI: 10.2147/ijgm.s266545] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 08/07/2020] [Indexed: 01/08/2023] Open
Abstract
Background Pharmacists being the drug experts need to be well aware of the applied handling of biosimilar medicines (BSMs). They are an integral educator, trailblazer, and advocate of biosimilar integration across all clinical settings. Therefore, the current study was conducted to assess the pharmacists’ knowledge, attitude, and practices of integrating BSMs into clinical practice. Methods The cross-sectional study was conducted from August 2019 to November 2019. The community pharmacies, clinical and academic settings in Karachi were approached for gathering the responses of pharmacists towards BSMs and interchangeable products using a 30-item survey form. Pearson correlation and independent sample t-test were used to identify the relationship among independent variables and the responses, considering p values <0.05 as statistically significant. Results Overall, there were 305 survey forms used with a response rate of 87.14%. More than 80% of the respondents have good knowledge about the definition, characteristics, safety and efficacy, compatibility, cost issues, and utilization of BSMs. Around half of the respondents (48.9%, [95% CI 46.6–51.2]) were confident in using BSMs in clinical practice. However, they were concerned about the BSM’s safety profile (45.2%, [95% CI 42.1–48.3]), quality (30.2%, [95% CI 28.3–32.1]), and efficacy issues (32.3%, [95% CI 31.2–37.5]). Conclusion The findings revealed that pharmacists were well informed about the BSMs. However, some of the responses to the attitude demonstrated a lack of understanding of the application of that knowledge. The respondents persuaded that advanced patterns of diseases, product marketing stipulations, and need for better patient care drives higher demand for developing BSMs and were enthusiastic about gaining more insight to integrate BSMs into routine clinical practice.
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Affiliation(s)
- Sadia Shakeel
- Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia.,Faculty of Pharmaceutical Sciences, Dow University of Health Sciences, Karachi, Pakistan
| | - Mohamed Azmi Hassali
- Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia
| | - Hina Rehman
- Institute of Pharmaceutical Sciences, Jinnah Sind Medical University, Karachi, Pakistan
| | - Anees Ur Rehman
- Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia.,Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Jaya Muneswarao
- Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia
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Schnorbach MT, Kruis W. [Cost of illness of inflammatory bowel disease in Germany]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 59:1173-1188. [PMID: 32869213 DOI: 10.1055/a-1174-0670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION The prevalence of inflammatory bowel disease (IBD) in Germany is rising. Due to a disease onset at a young age, direct and indirect costs are important. The aim of the present study is to provide a comprehensive presentation of existing healthcare costs for these diseases in Germany and to compare them by inflation adjustments for 2018. MATERIAL AND METHODS Performing a systematic literature search, monetary costs were extracted from German and English literature. Quality and relevance of the studies were assessed with a checklist. RESULTS The average outpatient cost for inflammatory bowel disease amounts between 18 and 87 Euro/pat/30 days, the average inpatient cost was between 1026 and 9083 Euro/case. Depending on the type of calculation, biologicals cause different amounts of cost. Few data are available for direct medical 82 and 618 Euro/pat/30 days, direct non-medical 63 and 84 Euro/pat/30 days and indirect costs 463 and 3493 Euro/pat/30 days. The total costs are about 533 Euro/pat/30 days, related to one year 6485 Euro/pat. CONCLUSION For the first time, it is possible to compare existing medical costs for IBD in Germany. Current studies feature very heterogeneous methods and study populations of IBD. Depending on the collective, the total costs are up to 6485 Euro/patient/year.
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Ascef BDO, Lopes ACDF, de Soárez PC. Health technology assessment of biosimilars worldwide: a scoping review. Health Res Policy Syst 2020; 18:95. [PMID: 32843051 PMCID: PMC7448328 DOI: 10.1186/s12961-020-00611-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 08/03/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Health technology assessment (HTA) should provide an assessment of a technology's effects on health and of the related social, economic, organisational and ethical issues. HTA reports on biosimilars can specifically assess their immunogenicity, their extrapolation to one or more conditions, and the risks of interchangeability and substitution. We aimed to complete a scoping review within the context of HTA organisations to synthesise HTA reports on biosimilars and to map the extension, scope and methodological practices. MAIN BODY A scoping review methodology was applied. The sources for biosimilars HTA reports were database searches and grey literature from HTA organisation websites up to June 2019. HTA reports of biosimilars were classified as full HTA, mini-HTA or rapid reviews. Data were extracted and recorded on a calibrated predefined data form. We identified 70 HTA reports of biosimilars of 16 biologic products (65.71% in 2015-2018) produced by 13 HTA organisations from 10 countries; 2 full HTAs, 4 mini-HTAs and 64 rapid reviews met the inclusion criteria. Almost all the rapid reviews gave no information regarding any evidence synthesis method and approximately half of the rapid reviews did not appraise the risk of bias of primary studies or the overall quality of evidence. All full-HTAs and mini-HTAs addressed organisational, ethical, social and legal considerations, while these factors were assessed in less than half of the rapid reviews. The immunogenicity and extrapolation of one or more conditions were often considered. The majority of full-HTAs and mini-HTAs contained an assessment of switching and a discussion of an educational approach about biosimilars. No HTA report rejected the adoption/reimbursement of the biosimilar assessed. CONCLUSION HTA of biosimilars are emerging in the context of HTA organisations and those that exist often duplicate reports of the same biosimilar. Most HTA reports of biosimilars do not conduct a systematic literature review or consider economic issues. No report has rejected the adoption/reimbursement of biosimilars. There is a need to standardise the minimum criteria for the development of HTA on biosimilars to ensure a better understanding and better decision-making.
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Affiliation(s)
- Bruna de Oliveira Ascef
- Preventive Medicine Department, Faculty of Medicine, The University of São Paulo, Av. Dr. Arnaldo, 455, sala 2228, São Paulo, SP CEP: 01246-903 Brazil
| | - Ana Carolina de Freitas Lopes
- Preventive Medicine Department, Faculty of Medicine, The University of São Paulo, Av. Dr. Arnaldo, 455, sala 2228, São Paulo, SP CEP: 01246-903 Brazil
| | - Patrícia Coelho de Soárez
- Preventive Medicine Department, Faculty of Medicine, The University of São Paulo, Av. Dr. Arnaldo, 455, sala 2228, São Paulo, SP CEP: 01246-903 Brazil
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Reynolds KA, Pithadia DJ, Lee EB, Liao W, Wu JJ. Safety and Effectiveness of Anti-Tumor Necrosis Factor-Alpha Biosimilar Agents in the Treatment of Psoriasis. Am J Clin Dermatol 2020; 21:483-491. [PMID: 32048187 DOI: 10.1007/s40257-020-00507-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Biologic drugs have revolutionized the treatment of psoriasis and other chronic inflammatory diseases. In recent years, many tumor necrosis factor-alpha 'biosimilar' agents have been developed. These biosimilars are similar in structure and function to their originator molecules, although they are not identical. Given that the safety and efficacy of the original biologic have already been proven, biosimilars are only required to show bioequivalence, or non-inferiority, to the reference biologic to be approved. Based on extrapolation of these non-inferiority data, biosimilars may be subsequently approved for all indications of the originator biologic, even without being directly studied in these various conditions. These biosimilar agents have been purported as a method to reduce the costs of biologic therapies, thereby increasing the accessibility of these medications and subsequently improving the treatment of psoriasis worldwide. The US Food and Drug Administration and/or the European Medicines Agency have approved biosimilars of adalimumab (Amjevita/Amgevita/Solymbic, Cyltezo, Imraldi/Hadlima, Hyrimoz/Hefiya/Halimatoz, Idacio, Hulio, Abrilada), etanercept (Erelzi, Benepali/Eticovo), and infliximab (Inflectra/Remsima, Renflexis/Flixabi, Ixifi/Zessly) for the treatment of psoriasis, and others are under review. There are many phase III data supporting the bioequivalence of these anti-tumor necrosis factor-alpha biosimilar agents in treating psoriasis and rheumatologic disease, which are discussed here. In general, these biosimilar agents have been shown to have equivalent efficacy, tolerability, and immunogenicity profiles compared to their originators in patients with rheumatologic disease, although studies in patients with psoriasis are fairly limited. Additional switching studies and post-marketing safety analyses are needed to assess the interchangeability of biosimilar agents with their reference products.
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Affiliation(s)
- Kelly A Reynolds
- College of Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Deeti J Pithadia
- Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Erica B Lee
- Department of Medicine, Santa Barbara Cottage Hospital, Santa Barbara, CA, USA
| | - Wilson Liao
- University of San Francisco, San Francisco, CA, USA
| | - Jashin J Wu
- Dermatology Research and Education Foundation, 4950 Barranca Pkwy, Suite 307, Irvine, CA, 92604, USA.
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20
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Perez T, Rico A, Boutière C, Maarouf A, Roudot M, Honoré S, Pelletier J, Bertault-Peres P, Audoin B. Comparison of rituximab originator (MabThera ®) to biosimilar (Truxima ®) in patients with multiple sclerosis. Mult Scler 2020; 27:585-592. [PMID: 32180508 DOI: 10.1177/1352458520912170] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Rituximab's originator MabThera® or Rituxan® has demonstrated high efficacy in multiple sclerosis (MS). Because of the patent expiration, rituximab biosimilars have been developed. However, because a biosimilar is not the exact copy of the originator, the efficacy and safety of a biosimilar may significantly differ. OBJECTIVES To compare the efficacy and safety of the biosimilar Truxima® and the originator MabThera® in MS. METHODS Consecutive MS patients receiving MabThera® or Truxima® were prospectively followed during 1 year after treatment introduction. Allocation to each treatment depended on the period of introduction and not the physician's choice. Lymphocyte count, clinical and magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS), and adverse events were compared. RESULTS In total, 105 and 40 patients received MabThera® and Truxima®, respectively. The two groups did not differ in baseline characteristics. Effect on CD19+ lymphocytes and disease activity were similar during follow-up. EDSS remained stable, with no difference between groups. Adverse events were similar between groups. CONCLUSION The efficacy and safety of the rituximab biosimilar Truxima® seem equivalent to the originator MabThera® in MS patients. Truxima® could represent a relatively cheap and safe therapeutic alternative to MabThera® and could improve access to highly efficient therapy for MS in low- or middle-income countries.
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Affiliation(s)
- Thomas Perez
- Service Pharmacie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France Institute of NeuroPhysiopathology (INP), CNRS, Aix-Marseille University, Marseille, France
| | - Audrey Rico
- Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France
| | - Clémence Boutière
- Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France
| | - Adil Maarouf
- Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France
| | - Marjorie Roudot
- Service Pharmacie, APHM, Hôpital de la Timone, Aix Marseille University, Marseille, France
| | - Stéphane Honoré
- Service Pharmacie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France Institute of NeuroPhysiopathology (INP), CNRS, Aix-Marseille University, Marseille, France
| | - Jean Pelletier
- Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France
| | - Pierre Bertault-Peres
- Service Pharmacie, APHM, Hôpital de la Timone, Aix Marseille University, Marseille, France
| | - Bertrand Audoin
- Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France
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Khan MA, Aseeri MA, Alshamrani MA, Alnatsheh AH, Alhamdan HS. Emerging Role of Biosimilars in Oncology-Hematology in Saudi Arabia: A Practical Perspective. ACTA ACUST UNITED AC 2019. [DOI: 10.4103/jqsh.jqsh_15_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Abstract
Biologics are significant drivers of globally escalating healthcare costs. Biosimilars have potential to offer cost savings with comparable efficacy and safety to innovator products and increase the access of treatment to more patients. This study aimed to increase understanding and perception of biosimilars concept. It also described the pharmacoeconomic impact of biosimilar in oncology and formulary consideration of oncology biosimilars substituting with their originators in major oncology centers in the Saudi Arabia. A biosimilar is a biological product that is similar to a reference biopharmaceutical product. As the manufacturing process hinders the ability to identically replicate the structure of the original product, biosimilar cannot be described as an absolute equivalent of the original medication. Different regulatory agencies such as United States Food and Drug Administration, European Medicines Agency, and Saudi Food and Drug Authority have approved several biosimilars of oncology biologics. The experience of biosimilar use in Europe and USA provides valuable insights into the use of biosimilars. The widespread use of biosimilars has the potential to reduce healthcare expenditure, as well as improving access without compromising patient outcomes. There is a need for increasing awareness about biosimilars to improve acceptance rates. The use of biosimilar filgrastim in Ministry of National Guard Health Affairs, Saudi Arabia, has resulted in a significant cost saving annually. It was proposed that further substitution and switching to biosimilars in oncology would lead to major savings in resources.
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Affiliation(s)
- Mansoor A. Khan
- Department of Pharmaceutical Care, King Abdulaziz Medical City – Western Region (KAMC-WR), Jeddah, Saudi Arabia, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mohammed A. Aseeri
- Department of Pharmaceutical Care, King Abdulaziz Medical City – Western Region (KAMC-WR), Jeddah, Saudi Arabia, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Majed A. Alshamrani
- Department of Pharmaceutical Care, King Abdulaziz Medical City – Western Region (KAMC-WR), Jeddah, Saudi Arabia, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Abdelmajid H. Alnatsheh
- Department of Pharmaceutical Care, King Abdulaziz Medical City – Western Region (KAMC-WR), Jeddah, Saudi Arabia, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Hani S. Alhamdan
- Department of Pharmaceutical Care, King Abdulaziz Medical City – Western Region (KAMC-WR), Jeddah, Saudi Arabia, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
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Konstantinidou S, Papaspiliou A, Kokkotou E. Current and future roles of biosimilars in oncology practice. Oncol Lett 2019; 19:45-51. [PMID: 31897113 PMCID: PMC6923870 DOI: 10.3892/ol.2019.11105] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 10/30/2019] [Indexed: 12/29/2022] Open
Abstract
Biologics have been used increasingly in the treatment and supportive care of cancer; however, their high cost places a significant burden on healthcare systems. The expiration of patents for biologics has led to the development of biosimilars, with the aim of reducing cost and increasing accessibility to novel treatments, which are affordable for a greater number of patients. Biosimilars are highly similar but not identical to the reference products; therefore, strict regulatory requirements have been formed for their approval. This ensures that there are no clinically meaningful differences compared with respective biologics, with regard to purity, safety and efficacy. In 2003, a regulatory framework for the approval of biosimilars was established in Europe, whereas the USA did not implement a framework until 2009, when the Biologics Price Competition and Innovation Act was formed. A number of biosimilars have currently been approved in oncology and the number is expected to rise in the near future. More than 10 years of evidence has revealed that biosimilars are safe and effective; however healthcare professionals need to be further educated to eliminate potential misconceptions and integrate biosimilars into routine clinical practice. The present review aims to provide an overview of the biosimilars used in Europe and the USA, present their main benefits and challenges, and discuss their current and future roles in medical oncology.
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Affiliation(s)
- Sofia Konstantinidou
- Oncology Unit, The Third Department of Medicine, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - Angeliki Papaspiliou
- Oncology Unit, The Third Department of Medicine, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - Eleni Kokkotou
- Oncology Unit, The Third Department of Medicine, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
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Abstract
Prior to the biologic era, the medical management of patients with inflammatory bowel disease (IBD) was dominated by the use of aminosalicylates, corticosteroids, and immunosuppressants. In the past two decades, the advent of biologic agents that target specific components of the immune response has greatly improved the care of patients with Crohn's disease and ulcerative colitis (UC). However, not all patients respond or maintain response to biologic therapy and some patients develop adverse events that necessitate treatment discontinuation. Furthermore, sensitization with formation of anti-drug antibodies is an inherent limitation to administration of monoclonal antibodies. This circumstance has generated renewed interest in the development of novel oral small-molecule drugs (SMDs) that are effective and well tolerated. Several classes of SMDs are currently progressing through the pipeline and offer the promise of oral delivery and high potency. In this review, we summarize different mechanisms of oral drug delivery to the gastrointestinal tract, highlight key findings from phase II and III randomized trials of novel oral SMDs, and discuss how oral SMDs are likely to be integrated into future IBD treatment paradigms. The most advanced development programs currently involve evaluation of compounds blocking Janus kinase (JAK) receptors or modulating sphingosine-1-phosphate (S1P) receptors. Tofacitinib, an oral JAK inhibitor, was recently approved for the treatment of moderate-to-severe UC. Several more selective JAK-1 inhibitors, including filgotinib and upadacitinib, have also shown positive results in phase II studies and are currently enrolling in phase III development programs. Similarly, ozanimod, an S1P1 and S1P5 receptor agonist, has shown early favorable results and is enrolling in phase III trials. As these and other novel oral SMDs come to market, several questions will need to be answered. The cost effectiveness, comparative treatment efficacy, predictors of response, and relative safety of oral SMDs compared to existing therapies will need to be evaluated. Given the modest efficacy rates observed with both biologic therapies and novel SMDs to date, the potential for combination therapy based on a non-sensitizing oral option is promising and may be facilitated by development of organ-specific therapies with pharmacodynamic activity restricted to the gut to minimize systemic toxicity.
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Yang J, Yu S, Yang Z, Yan Y, Chen Y, Zeng H, Ma F, Shi Y, Shi Y, Zhang Z, Sun F. Efficacy and Safety of Anti-cancer Biosimilars Compared to Reference Biologics in Oncology: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. BioDrugs 2019; 33:357-371. [PMID: 31175632 DOI: 10.1007/s40259-019-00358-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Many biosimilars of monoclonal antibodies (mAbs) are becoming increasingly available as anticancer therapies, such as the rituximab, bevacizumab, and trastuzumab biosimilars. However, no comprehensive summary of their efficacy and safety is available. OBJECTIVE This study synthesized current evidence on the efficacy and safety of mAb biosimilars relative to their reference biologics among cancer patients. METHODS We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, the ISI Web of Science, and several Chinese databases from their inception dates to December 31, 2018, for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of biosimilars with reference biologics used in oncology. The binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs), continuous outcomes using weighted mean difference (WMD) with 95% CIs, and time-to-event outcomes using hazard ratios (HRs). Subgroup and sensitivity analyses were conducted following this. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the evidence. RESULTS We did not find any comparative observational studies that fit the criteria. Twenty-three RCTs were identified for biosimilars of three mAbs, of which eight RCTs examined rituximab biosimilars (total N = 1534), six RCTs were for bevacizumab biosimilars (total N = 1897), and nine were for trastuzumab biosimilars (total N = 4953), respectively. The quality of the GRADE evidence for efficacy and safety outcomes was moderate or low. The findings were robust for all pre-specified subgroup and sensitivity analyses. CONCLUSION The existing evidence suggests highly comparable efficacy and safety profiles between mAb biosimilars and their reference biologics in oncological drugs.
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Affiliation(s)
- Jichun Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Shuqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Zhirong Yang
- Primary Care Unit, School of Clinical Medicine, University of Cambridge, Cambridgeshire, CB18RN, UK
| | - Yusong Yan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Yao Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Hongmei Zeng
- Department of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yanxia Shi
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center/State Key Laboratory of Oncology in South China/Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Yehui Shi
- Phase I Clinical Trial Department of Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Zilu Zhang
- Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
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Brekkan A, Lopez-Lazaro L, Plan EL, Nyberg J, Kankanwadi S, Karlsson MO. Sensitivity of Pegfilgrastim Pharmacokinetic and Pharmacodynamic Parameters to Product Differences in Similarity Studies. AAPS JOURNAL 2019; 21:85. [PMID: 31286293 PMCID: PMC6614128 DOI: 10.1208/s12248-019-0349-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 05/30/2019] [Indexed: 11/30/2022]
Abstract
In this work, a previously developed pegfilgrastim (PG) population pharmacokinetic-pharmacodynamic (PKPD) model was used to evaluate potential factors of importance in the assessment of PG PK and PD similarity. Absolute neutrophil count (ANC) was the modelled PD variable. A two-way cross-over study was simulated where a reference PG and a potentially biosimilar test product were administered to healthy volunteers. Differences in delivered dose amounts or potency between the products were simulated. A different baseline absolute neutrophil count (ANC) was also considered. Additionally, the power to conclude PK or PD similarity based on areas under the PG concentration-time curve (AUC) and ANC-time curve (AUEC) were calculated. Delivered dose differences between the products led to a greater than dose proportional differences in AUC but not in AUEC, respectively. A 10% dose difference from a 6 mg dose resulted in 51% and 7% differences in AUC and AUEC, respectively. These differences were more pronounced with low baseline ANC. Potency differences up to 50% were not associated with large differences in either AUCs or AUECs. The power to conclude PK similarity was affected by the simulated dose difference; with a 4% dose difference from 6 mg the power was approximately 29% with 250 subjects. The power to conclude PD similarity was high for all delivered dose differences and sample sizes.
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Affiliation(s)
- Ari Brekkan
- Pharmetheus, Uppsala, Sweden.,Pharmacometrics Research Group, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
| | | | | | | | | | - Mats O Karlsson
- Pharmetheus, Uppsala, Sweden. .,Pharmacometrics Research Group, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
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Abstract
OBJECTIVES To assess the degree of readability and the length of the package leaflets of biosimilars. SETTING The package leaflets analysed were downloaded from the European Medicines Agency (EMA) website. PARTICIPANTS The study sample included the package leaflets written in English of all the biosimilars that were authorised by the EMA on 31 August 2017, and whose content was available via the internet on that date (n=35). DESIGN This was a cross-sectional analytical study. The readability of the package leaflets of all biosimilars authorised by the EMA in August 2017 was determined applying the Flesch and Flesch-Kincaid formulas. The influence of the following variables on the readability and length was also analysed: package leaflet section, type of biosimilar, date of first authorisation of the biosimilar and type of medicine. RESULTS A considerable variation of the package leaflets length was found (3154±803). The readability of all the package leaflets overtook the recommended value for health-related written materials taking into account Flesch-Kincaid Index, and none of the package leaflets were easy to understand according to the Flesch Index. Statistically significant differences (p<0.05) were observed between the sections of package leaflets in readability indices and length. The most difficult sections to understand were those related with the therapeutic indication of medicine and the possible side effects. CONCLUSIONS Package leaflets for authorised biosimilars may not fulfil the function for which they were designed. The competent organisations could be informed about the possible negative effect on the use of this type of medicines.
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Affiliation(s)
- María Ángeles Piñero-López
- Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
| | - Carlos Figueiredo-Escribá
- Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
| | - Pilar Modamio
- Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
| | - Cecilia F Lastra
- Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
| | - Eduardo L Mariño
- Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
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Santoleri F, Romagnoli A, Costantini A. Use and costs of originator and biosimilar erythropoiesis-stimulating agents in the treatment of chemotherapy-induced anemia: real-world evidence from an Italian hospital. Future Oncol 2019; 15:45-51. [DOI: 10.2217/fon-2018-0333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The aim of this retrospective study is to evaluate adherence, switch and costs a year after the start of treatment with different erythropoietin-stimulating agents. There were 277 patients, 200 were originators (72.20%) and 77 (27.80%) were biosimilars. Adherence to treatment for originators is 0.84 ± 0.22 versus 0.76 ± 0.27 for biosimilars (p = 0.3241). Medication adherence was calculated as ratio between received daily dose to prescribed daily dose. The optimum value is 1, values less than 1 indicate loss of adherence. The cost of treatment per year is €7365 per patient for the use of the originator drug versus €2587 for biosimilars, with a difference of €4777 per patient.
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Link BK. Biosimilars: when a negative study can be positive. Lancet Haematol 2018; 5:e500-e501. [PMID: 30389032 DOI: 10.1016/s2352-3026(18)30172-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 09/26/2018] [Indexed: 06/08/2023]
Affiliation(s)
- Brian K Link
- Department of Internal Medicine, University of Iowa Hospitals, Iowa City, Iowa 52242, USA.
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Patel KB, Arantes LH, Tang WY, Fung S. The role of biosimilars in value-based oncology care. Cancer Manag Res 2018; 10:4591-4602. [PMID: 30410395 PMCID: PMC6199968 DOI: 10.2147/cmar.s164201] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Biopharmaceuticals (biologics) represent one of the fastest growing sectors of cancer treatment. They are recommended for treating underlying cancer and as supportive care for management of treatment side effects. Given the high costs of cancer care and the need to balance health care provision and associated budgets, patient access and value are the subject of discussion and debate in the USA and globally. As the costs of biologics are high, biosimilars offer the potential of greater choice and value, increased patient access to treatment, and the potential for improved outcomes. Value-based care aims to improve the quality of care, while containing costs. The Centers for Medicare & Medicaid Services (CMS) has developed value-based care programs as alternatives to fee-for-service reimbursement, including in oncology, that reward health care providers with incentive payments for improving the quality of care they provide. It is anticipated that CMS payments in oncology care will be increasingly tied to measured performance. This review provides an overview of value-based care models in oncology with a focus on CMS programs and discusses the contribution of biosimilars to CMS value-based care objectives. Biosimilars may provide an important tool for providers participating in value-based care initiatives, resulting in cost savings and efficiencies in the delivery of high-value care through expanded use of biologic treatment and supportive care agents during episodes of cancer care.
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Affiliation(s)
| | - Luiz H Arantes
- Biosimilars Global Medical Affairs, Pfizer Essential Health, Pfizer Inc. New York, NY, USA
| | - Wing Yu Tang
- Health Economics and Outcomes Research, Pfizer Health & Impact, Pfizer Essential Health, Pfizer Inc. New York, NY, USA
| | - Selwyn Fung
- Pfizer Essential Health Research & Development, Pfizer Inc. New York, NY, USA,
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Husereau D, Feagan B, Selya-Hammer C. Policy Options for Infliximab Biosimilars in Inflammatory Bowel Disease Given Emerging Evidence for Switching. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2018; 16:279-288. [PMID: 29411318 PMCID: PMC5940725 DOI: 10.1007/s40258-018-0371-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Biosimilars are becoming increasingly available internationally as patents expire on the originator biologic drugs they are intended to copy. Although substitution policies seen with generic drugs are being considered as a means to reduce expenditures on biologics, some biosimilars pose particular challenges in that the act of substitution may eventually lead to increased rates of therapeutic failure. As evidence requirements from regulators do not directly address this challenge, switch trials of biosimilars have emerged that may provide further answers. Using infliximab in inflammatory bowel disease as an example, we critically examine emerging evidence from two key switch trials (NOR-SWITCH and NCT020968610) and discuss the clinical and economic implications of these and what policy options may be most reasonable for payers. Options include reimbursing biosimilars for only newly diagnosed patients, using product-listing agreements to manage uncertainty, or using tiered co-payments or other incentives to promote biosimilar use.
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Affiliation(s)
- Don Husereau
- School of Epidemiology and Public Health, University of Ottawa, Room 101, 600 Peter Morand Crescent, Ottawa, ON, K1G 5Z3, Canada.
| | - Brian Feagan
- Robarts Clinical Trials, Robarts Research, University of Western Ontario, London, Canada
- Department of Medicine, University of Western Ontario, London, Canada
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada
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Thennati R, Singh SK, Nage N, Patel Y, Bose SK, Burade V, Ranbhor RS. Analytical characterization of recombinant hCG and comparative studies with reference product. Biologics 2018; 12:23-35. [PMID: 29430170 PMCID: PMC5796461 DOI: 10.2147/btt.s141203] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Regulatory agencies recommend a stepwise approach for demonstrating biosimilarity between a proposed biosimilar and reference biological product emphasizing for functional and structural characterization to trace if there is any difference which may impact safety and efficacy. We studied the comparative structural and biological attributes of recombinant human chorionic gonadotropin (rhCG), SB005, with reference product, Ovidrel® and Ovitrelle®. Recombiant hCG was approved in 2000 by the US Food and Drug Administration for the induction of final follicular maturation, early luteinization in infertile women as part of assisted reproductive technology program. It is also indicated for the induction of ovulation and pregnancy in ovulatory infertile patients whose cause of infertility is not due to ovarian failure. MATERIALS AND METHODS Primary structure was studied by intact mass analysis, peptide fingerprinting, peptide mass fingerprinting and sequence coverage analysis. Higher order structure was studied by circular dichroism, ultraviolet-visible spectroscopy, fluorescence spectroscopy, and disulfide bridge analysis. Different isoforms of reference product and SB005 were identified using capillary isoelectric focusing and capillary zone electrophoresis. Glycosylation was studied by N-glycan mapping using LC-ESI-MS, point of glycosylation, released glycan analysis using ultra performance liquid chromatography and sialic acid analysis. Product related impurities such as oligomer content analysis and oxidized impurities were studied using size exclusion chromatography and reverse phase high performance liquid chromatography, respectively. Biological activity in term of potency of reference product and SB005 was studied by in vivo analysis. RESULTS AND CONCLUSION In this study we have compared analytical similarity of recombinant rhCG (SB005) produced at Sun Pharmaceuticals with the reference product with respect to its primary, higher order structure, isoforms, charge variants, glycosylation, sialyation pattern, pharmacodynamic and in vivo efficacy. Our studies show that the in house produced rhCG has a high degree of structural and functional similarity with the reference product available in the market.
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Affiliation(s)
| | | | | | | | | | - Vinod Burade
- Sun Pharmaceutical Advanced Research Center, Vadodara, Gujarat, India
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Farhat F, Torres A, Park W, de Lima Lopes G, Mudad R, Ikpeazu C, Abi Aad S. The Concept of Biosimilars: From Characterization to Evolution-A Narrative Review. Oncologist 2017; 23:346-352. [PMID: 29284760 DOI: 10.1634/theoncologist.2017-0126] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Accepted: 09/26/2017] [Indexed: 02/07/2023] Open
Abstract
Biologic agents are currently the fastest emerging segment of drug expenditure. Unlike chemically synthesized small-molecule drugs, biologics are more complex, medicinal products produced by a living organism. They have become part of the standard of care in the treatment of a large variety of diseases, such as growth disorders, autoimmune diseases, cancer, cardiovascular illnesses, hemophilia, and rare genetic conditions, to name a few. Biosimilars, which are copies of biologics that are highly similar, were introduced in the market with an aim to offer efficacy that is not clinically different from the originator or reference product, at lower prices. We aim to clarify the concept of biosimilar, from definitions, history, market entry, challenges faced, and future evolution. For that purpose, we performed a literature search on the sites of the medicines regulatory agencies and PubMed from 1990 to 2014 with the keywords "biosimilars," "market," and "regulatory." In 2006, the first biosimilar, somatropin [rDNA origin], was marketed and led the way for biosimilar drug manufacturing. As a result, manufacturers have entered a diversified competition, facing challenges in manufacturing these complex agents, such as immunogenicity and efficiency. Biosimilars are set to evolve differently in various markets, namely the U.S., Japan, the European Union, and the "pharmerging" economies. IMPLICATIONS FOR PRACTICE This article highlights the importance of biosimilars, as a cost-cutting strategy, in the delivery of state-of-the-art health care in developing countries, at a fraction of what a reference biological agent would cost.
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Affiliation(s)
- Fadi Farhat
- Department of Hematology-Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon
| | - Alfredo Torres
- Department of Hematology-Oncology, University of Miami-Sylvester Comprehensive Cancer Center, Miami, Florida, USA
| | - Wungki Park
- Department of Hematology-Oncology, University of Miami-Sylvester Comprehensive Cancer Center, Miami, Florida, USA
| | - Gilberto de Lima Lopes
- Department of Hematology-Oncology, University of Miami-Sylvester Comprehensive Cancer Center, Miami, Florida, USA
| | - Raja Mudad
- Department of Hematology-Oncology, University of Miami-Sylvester Comprehensive Cancer Center, Miami, Florida, USA
| | - Chukwuemeka Ikpeazu
- Department of Hematology-Oncology, University of Miami-Sylvester Comprehensive Cancer Center, Miami, Florida, USA
| | - Simon Abi Aad
- Department of Hematology-Oncology, University of Miami-Sylvester Comprehensive Cancer Center, Miami, Florida, USA
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Simoens S, Jacobs I, Popovian R, Isakov L, Shane LG. Assessing the Value of Biosimilars: A Review of the Role of Budget Impact Analysis. PHARMACOECONOMICS 2017; 35:1047-1062. [PMID: 28660473 PMCID: PMC5606961 DOI: 10.1007/s40273-017-0529-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Biosimilar drugs are highly similar to an originator (reference) biologic, with no clinically meaningful differences in terms of safety or efficacy. As biosimilars offer the potential for lower acquisition costs versus the originator biologic, evaluating the economic implications of the introduction of biosimilars is of interest. Budget impact analysis (BIA) is a commonly used methodology. This review of published BIAs of biosimilar fusion proteins and/or monoclonal antibodies identified 12 unique publications (three full papers and nine congress posters). When evaluated alongside professional guidance on conducting BIA, the majority of BIAs identified were generally in line with international recommendations. However, a lack of peer-reviewed journal articles and considerable shortcomings in the publications were identified. Deficiencies included a limited range of cost parameters, a reliance on assumptions for parameters such as uptake and drug pricing, a lack of expert validation, and a limited range of sensitivity analyses that were based on arbitrary ranges. The rationale for the methods employed, limitations of the BIA approach, and instructions for local adaptation often were inadequately discussed. To understand fully the potential economic impact and value of biosimilars, the impact of biosimilar supply, manufacturer-provided supporting services, and price competition should be included in BIAs. Alternative approaches, such as cost minimization, which requires evidence demonstrating similarity to the originator biologic, and those that integrate a range of economic assessment methods, are needed to assess the value of biosimilars.
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Affiliation(s)
- Steven Simoens
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Ira Jacobs
- Global Medical Affairs, Pfizer Inc., 235 East 42nd Street, New York, NY, 10017-5755, USA.
| | | | | | - Lesley G Shane
- Outcomes and Evidence, Global Health and Value, Pfizer Inc., New York, NY, USA
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Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother 2017; 13:1972-1988. [PMID: 28841363 PMCID: PMC5612212 DOI: 10.1080/21645515.2017.1316909] [Citation(s) in RCA: 202] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 03/26/2017] [Accepted: 03/31/2017] [Indexed: 12/11/2022] Open
Abstract
Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA). This article provides an overview of TCZ including looking into the past at the discovery of interleukin-6 (IL-6) as a pro-inflammatory cytokine. It also looks at how tocilizumab was developed, manufactured and tested to ensure both safety and efficacy in a human population. The article then explores the advantages and disadvantages of using TCZ when compared to other biologics approved in RA, sJIA and pJIA and finally looks ahead to the future and the emerging role of IL-6 and its blockade by TCZ as a treatment for giant cell arteritis (GCA), polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV).
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MESH Headings
- Animals
- Antibodies, Monoclonal, Humanized/adverse effects
- Antibodies, Monoclonal, Humanized/pharmacokinetics
- Antibodies, Monoclonal, Humanized/therapeutic use
- Arthritis, Rheumatoid/drug therapy
- Arthritis, Rheumatoid/immunology
- Drug Approval
- Humans
- Interleukin-6/immunology
- Polymyalgia Rheumatica/drug therapy
- Receptors, Interleukin-6/antagonists & inhibitors
- Receptors, Interleukin-6/immunology
- Vasculitis/drug therapy
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Affiliation(s)
- Martin Sheppard
- Southend University Hospital NHS Foundation Trust, Westcliff on Sea, UK
| | - Faidra Laskou
- Southend University Hospital NHS Foundation Trust, Westcliff on Sea, UK
| | | | - Shahryar Hadavi
- Southend University Hospital NHS Foundation Trust, Westcliff on Sea, UK
| | - Bhaskar Dasgupta
- Southend University Hospital NHS Foundation Trust, Westcliff on Sea, UK
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Abstract
Biologics play a key role in cancer treatment and are principal components of many therapeutic regimens. However, they require complex manufacturing processes, resulting in high cost and occasional shortages in supply. The cost of biologics limits accessibility of cancer treatment for many patients. Effective and affordable cancer therapies are needed globally, more so in developing countries, where health care resources can be limited. Biosimilars, which have biologic activity comparable to their corresponding reference drugs and are often more cost effective, have the potential to enhance treatment accessibility for patients and provide alternatives for decision makers (ie, prescribers, regulators, payers, policymakers, and drug developers). Impending patent expirations of several oncology biologics have opened up a vista for the development of corresponding biosimilars. Several countries have implemented abbreviated pathways for approval of biosimilars; however, challenges to their effective use persist. Some of these include designing appropriate clinical trials for assessing biosimilarity, extrapolation of indications, immunogenicity, interchangeability with the reference drug, lack of awareness and possibly acceptance among health care providers, and potential political barriers. In this review, we discuss the potential role and impact of biosimilars in oncology and the challenges related to their adoption and use. We also review the safety and efficacy of some of the widely used biosimilars in oncology and other therapeutic areas (eg, bevacizumab, darbepoetin, filgrastim, rituximab, and trastuzumab).
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Affiliation(s)
- Rakesh Chopra
- , Artemis Cancer Institute, Artemis Hospitals, Gurgaon, Haryana, India; and , Sylvester Comprehensive Cancer Center at the University of Miami, Miami, FL
| | - Gilberto Lopes
- , Artemis Cancer Institute, Artemis Hospitals, Gurgaon, Haryana, India; and , Sylvester Comprehensive Cancer Center at the University of Miami, Miami, FL
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Stavrik-Genadieva S, Grozdanova A, Netkovska-Ancevska K, Dimitrova-Genadieva M, Dimitrov G. Regulatory considerations of biosimilars and clinical dilema of their use. SANAMED 2017. [DOI: 10.24125/sanamed.v1i1.158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Biomedical products are complex molecules, produced by living cells. More accurately, they are molecules that are naturally produced in the human body, like hormones or growth factors, monoclonal antibodies, blood products, immunological medicinal products, sera and vaccines, allergens, and advanced technology products such as gene and cell therapy products. Copies of these drugs, known as biosimilars, are comparable but not identical and are not generic version of innovator biological products. Specific regulatory requirements and abbreviated registration process apply in the case of biosimilars, in order to demonstrate efficacy and safety profile and to prove that product is similar to the original biomedical product. Like all medicines, biological medicines work by interacting with the body to produce a therapeutic outcome, but the mechanisms by which they do this may vary from product to product and through indications. Therefore the role of the physicians in treatment of patients with these complex medicinal products is particularly important. Regulatory issues, manufacturing, safety, physicians have part in develop use of biosimilars as much as generic drugs. Even though, the most important factor for market of biosimilar are commercial factor, still, real clinical dilemma of use are present, so it is necessary to have clear regulatory framework and postmarketing data on the use of biosimilars.
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Understanding the biosimilar approval and extrapolation process—A case study of an epoetin biosimilar. Crit Rev Oncol Hematol 2016; 104:98-107. [DOI: 10.1016/j.critrevonc.2016.04.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 04/01/2016] [Accepted: 04/27/2016] [Indexed: 11/20/2022] Open
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Araújo FC, Gonçalves J, Fonseca JE. Pharmacoeconomics of Biosimilars: What Is There to Gain from Them? Curr Rheumatol Rep 2016; 18:50. [DOI: 10.1007/s11926-016-0601-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Cost-Effectiveness of Cetuximab for Advanced Esophageal Squamous Cell Carcinoma. PLoS One 2016; 11:e0153943. [PMID: 27100871 PMCID: PMC4839693 DOI: 10.1371/journal.pone.0153943] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 04/06/2016] [Indexed: 01/09/2023] Open
Abstract
Background Costly biologicals in palliative oncology are emerging at a rapid pace. For example, in patients with advanced esophageal squamous cell carcinoma addition of cetuximab to a palliative chemotherapy regimen appears to improve survival. However, it simultaneously results in higher costs. We aimed to determine the incremental cost-effectiveness ratio of adding cetuximab to first-line chemotherapeutic treatment of patients with advanced esophageal squamous cell carcinoma, based on data from a randomized controlled phase II trial. Methods A cost effectiveness analysis model was applied based on individual patient data. It included only direct medical costs from the health-care perspective. Quality-adjusted life-years and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by a Monte Carlo analysis. Results Adding cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma resulted in an the incremental cost-effectiveness ratio of €252,203 per quality-adjusted life-year. Sensitivity analysis shows that there is a chance of less than 0.001 that the incremental cost-effectiveness ratio will be less than a maximum willingness to pay threshold of €40,000 per quality-adjusted life-year, which is representative for the threshold used in The Netherlands and other developed countries. Conclusions Addition of cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma is not cost-effective when appraised according to currently accepted criteria. Cost-effectiveness analyses using outcome data from early clinical trials (i.c. a phase II trial) enable pharmaceutical companies and policy makers to gain early insight into whether a new drug meets the current eligibility standards for reimbursement and thereby potential admittance for use in regular clinical practice.
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Harenberg J, Cimminiello C, Agnelli G, Di Minno G, Polo Friz H, Prandoni P, Scaglione F. Biosimilars of low-molecular-weight heparin products: fostering competition or reducing 'biodiversity'? J Thromb Haemost 2016; 14:421-6. [PMID: 26711899 DOI: 10.1111/jth.13237] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Indexed: 11/29/2022]
Abstract
The term 'biosimilars' is used to qualify products developed to be similar to an original biological drug. Biosimilars are much more complicated to develop than a generic version of small-molecule drugs and this is especially true for low-molecular-weight heparins (LMWHs). Evidence on the antithrombotic management of acute coronary syndromes (ACS) showed that the introduction into the market of biosimilars approved on the basis of simple biological criteria, without robust data from comparative clinical trials, may be hazardous. Moreover, the mixtures of LMWH polysaccharide chains, some immunoallergic properties and potential contamination during the extraction process raise safety concerns. As was the case for the biosimilar erythropoietin, there is the risk that only copies of the most commercially successful LMWHs will be marketed, thus jeopardizing the 'biodiversity' now ensured by the presence of several LMWHs, each with unique features that support the use of an individual LMWH as first-choice therapy in certain categories of patients.
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Affiliation(s)
- J Harenberg
- Clinical Pharmacology, Medical Faculty Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany
| | - C Cimminiello
- Department of Medicine, Vimercate Hospital Azienda Ospedaliera di Desio e Vimercate, Vimercate, Italy
| | - G Agnelli
- Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy
| | - G Di Minno
- Department of Clinical and Experimental Medicine, Federico II University Hospital, Naples, Italy
| | - H Polo Friz
- Department of Medicine, Vimercate Hospital Azienda Ospedaliera di Desio e Vimercate, Vimercate, Italy
| | - P Prandoni
- Department of Cardiothoracic and Vascular Sciences, Clinica Medica 2, University of Padua, Padua, Italy
| | - F Scaglione
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Neumann D, Jabłecka A. Reimbursement of biosimilars in Poland: is there a link to health technology assessment? Expert Rev Pharmacoecon Outcomes Res 2016; 16:781-792. [DOI: 10.1586/14737167.2016.1141051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
| | - Anna Jabłecka
- Department of Clinical Pharmacology, Poznan University of Medical Sciences, Poznan, Poland
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Mitropoulou C, Fragoulakis V, Bozina N, Vozikis A, Supe S, Bozina T, Poljakovic Z, van Schaik RH, Patrinos GP. Economic evaluation of pharmacogenomic-guided warfarin treatment for elderly Croatian atrial fibrillation patients with ischemic stroke. Pharmacogenomics 2016; 16:137-48. [PMID: 25616100 DOI: 10.2217/pgs.14.167] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND & METHODS Economic evaluation in genomic medicine is an emerging discipline to assess the cost-effectiveness of genome-guided treatment. Here, we developed a pharmaco-economic model to assess whether pharmacogenomic (PGx)-guided warfarin treatment of elderly ischemic stroke patients with atrial fibrillation in Croatia is cost effective compared with non-PGx therapy. The time horizon of the model was set at 1 year. RESULTS Our primary analysis indicates that 97.07% (95% CI: 94.08-99.34%) of patients belonging to the PGx-guided group have not had any major complications, compared with the control group (89.12%; 95% CI: 84.00-93.87%, p < 0.05). The total cost per patient was estimated at €538.7 (95% CI: €526.3-551.2) for the PGx-guided group versus €219.7 (95% CI: €137.9-304.2) for the control group. In terms of quality-adjusted life-years (QALYs) gained, total QALYs was estimated at 0.954 (95% CI: 0.943-0.964) and 0.944 (95% CI: 0.931-0.956) for the PGx-guided and the control groups, respectively. The true difference in QALYs was estimated at 0.01 (95% CI: 0.005-0.015) in favor of the PGx-guided group. The incremental cost-effectiveness ratio of the PGx-guided versus the control groups was estimated at €31,225/QALY. CONCLUSION Overall, our data indicate that PGx-guided warfarin treatment may represent a cost-effective therapy option for the management of elderly patients with atrial fibrillation who developed ischemic stroke in Croatia.
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Affiliation(s)
- Christina Mitropoulou
- Department of Clinical Chemistry, Faculty of Medicine & Health Sciences, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
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Guertin JR, Mitchell D, Ali F, LeLorier J. Bias within economic evaluations - the impact of considering the future entry of lower-cost generics on currently estimated incremental cost-effectiveness ratios of a new drug. CLINICOECONOMICS AND OUTCOMES RESEARCH 2015; 7:497-503. [PMID: 26504402 PMCID: PMC4605233 DOI: 10.2147/ceor.s90386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Most economic evaluation models compare a new patented drug (NPRx) to a generic comparator. Drug costs within these models are usually limited to the retail cost of both drugs at the time of model conception. However, the retail cost of the NPRx is expected to drop once generic versions of this molecule are introduced following the expiration of the NPRx’s patent. The objective of this study was to examine the impact on the incremental cost-effectiveness ratio (ICER) of the future introduction of lower-cost generic versions of the NPRx within the model’s time horizon. Methods We examined the impact of this parameter with the use of two approaches: 1) a mathematical proof identifying its impact on the NPRx’s ICER; and 2) applying this parameter to a previously published economic model comparing a NPRx to a generic comparator and identifying what would have been the NPRx’s ICER had this model considered this parameter. Results As expected, both the mathematical proof and the application to the previously published economic model showed that considering the future introduction of lower-cost generic versions of the NPRx within the model’s time horizon lowers the NPRx’s ICER. The timing of the future entry of lower-cost generic molecules, their relative price compared to that of the patented version, and the discount rate applied to future costs all influenced the results. Conclusion An ICER estimated within economic evaluations comparing NPRx to generic comparators which ignore the future introduction of lower-cost generic versions of the NPRx within the model’s time horizon will tend to be overestimated. Inclusion of this parameter should be considered within future economic evaluations.
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Affiliation(s)
- Jason R Guertin
- CHUM Research Center, Montréal, QC, Canada ; Programs for Assessment of Health Technology in Health Research Institute, Hamilton, ON, Canada
| | - Dominic Mitchell
- CHUM Research Center, Montréal, QC, Canada ; Logimétrix Inc., Repentigny, QC, Canada
| | - Farzad Ali
- Pfizer Canada Inc., Kirkland, QC, Canada
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Ventola CL. Evaluation of Biosimilars for Formulary Inclusion: Factors for Consideration by P&T Committees. P & T : A PEER-REVIEWED JOURNAL FOR FORMULARY MANAGEMENT 2015; 40:680-689. [PMID: 26535024 PMCID: PMC4606858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
P&T committees will play a key role in driving the adoption of biosimilars, which have unique characteristics compared with small-molecule generic drugs. Key elements of formulary review will include clinical parameters, product characteristics, and institutional considerations, which are among the issues covered in this article.
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Declerck P, Farouk-Rezk M, Rudd PM. Biosimilarity Versus Manufacturing Change: Two Distinct Concepts. Pharm Res 2015; 33:261-8. [DOI: 10.1007/s11095-015-1790-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 09/02/2015] [Indexed: 12/23/2022]
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Safety profile of biological medicines as compared with non-biologicals: an analysis of the italian spontaneous reporting system database. Drug Saf 2015; 37:961-70. [PMID: 25255847 DOI: 10.1007/s40264-014-0224-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
BACKGROUND Biologicals are important treatment options for various chronic diseases. After the introduction of the first biosimilars, animated debate arose in the scientific community about the actual benefit-risk profile of these drugs. In this context, a comparative safety evaluation of biologicals and biosimilars in clinical practice is warranted. METHODS We identified all suspected adverse drug reactions (ADRs) concerning biological/biosimilars (excluding vaccines, toxins, blood derivatives, and radio-pharmaceuticals), and further classified them into mechanistic classes. We described the frequency of biological/biosimilar class- and compound-specific ADRs by system organ class (SOC) and type of reporter. We also separately explored the traceability of biologicals and biosimilar-related ADR reports. RESULTS Overall 171,201 ADR reports were collected during the observation period; 9,601 (5.6 %) of these concerned biologicals. Biological-related reports were mainly issued by hospital-based physicians (78.7 %). Most of these reports involved monoclonal antibodies and fusion proteins (66.3 %). Reported ADRs were mainly 'skin and subcutaneous tissue disorders' (21 %), 'general and administration site disorders' (17 %), and 'gastrointestinal disorders' (13.6 %). In terms of traceability, 94.8 % of biological-related reports included an identifiable product name, whilst only 8.6 % indicated the corresponding batch number. Regarding biosimilars, 298 reports were identified, with a low proportion indicating drug ineffectiveness (10.1 %). CONCLUSIONS Most ADRs attributed to biologicals are 'skin and subcutaneous tissue disorders'. Anticancer monoclonal antibodies are most frequently associated with ADRs. A low proportion of ADR reports concern biosimilars.
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Abstract
Biosimilar agents are approximate copies of branded biologic therapies. Since the first biosimilar was authorized in the European Union in 2006, fifteen additional agents have been approved by the European Medicines Agency, including two biosimilar monoclonal antibodies (mAbs). Biosimilar mAbs represent a distinct class given their large molecular size, complex protein structure, and post-translational modifications. While guidelines have been established for the development, approval, and use of biosimilars, further scrutiny and discussion is necessary to fully understand their potential impact on clinical outcomes. This review takes a critical look at the structural complexity of biosimilar mABs, the feasibility of indication extrapolation, the impact of product variability on immunogenicity, the importance of comprehensive pharmacovigilance, and the potential for ongoing pharmacoeconomic impact.
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Affiliation(s)
- Håkan Mellstedt
- Professor of Oncological Biotherapy, Department of Oncology-Pathology, Karolinska Institute, SE-171 76 Stockholm, Sweden
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Abstract
A biosimilar drug or follow-on biologic drug is defined by the Public Health Service Act as a product that is "highly similar to the reference product notwithstanding minor differences in clinically active components and there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity and potency of the product." The advantage of biosimilar drugs is that they are significantly less expensive than the reference products, allowing for increased accessibility and cost savings. Recognizing these advantages, the US Congress passed the Biologics Price Competition and Innovation Act in 2009 as part of health care reform. The Biologics Price Competition and Innovation Act allows sponsors of biosimilar agents to seek approval by showing structural and functional similarity to the reference agent, with the extent of required clinical studies to be determined on the basis of the degree of biosimilarity with the reference product. The goal is to bring biosimilar agents to the market more efficiently while still protecting the safety of the public. The European Union has had such a process in place for a number of years. Two biosimilar epoetin agents have been approved in the European Union since 2007, and their companies are conducting trials to seek approval in the United States, because Amgen's patent protection for epoetin alfa expires in 2014. Trials completed for European Union approval of both agents showed similar efficacy and safety to the reference epoetin alfa. As with all biologics, immunogenicity concerns may persist because of the fragility of the manufacturing process and the worldwide experience with pure red cell aplasia as a result of epoetin therapy. The uptake of biosimilar epoetins after approval in the United States will depend on the balance of cost advantage against safety concerns. Competition in the marketplace will likely decrease the cost of the reference agent as well.
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Affiliation(s)
- Jay B Wish
- Department of Medicine, Division of Nephrology, Indiana University Health, Indianapolis, Indiana
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Davis-Ajami ML, Wu J, Downton K, Ludeman E, Noxon V. Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility. Biologics 2014; 8:155-67. [PMID: 24790409 PMCID: PMC3999275 DOI: 10.2147/btt.s27578] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L) or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L). This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility.
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Affiliation(s)
- Mary Lynn Davis-Ajami
- Organizational Systems and Adult Health, University of Maryland School of Nursing, Baltimore, MD, USA
| | - Jun Wu
- South Carolina College of Pharmacy, University of South Carolina, Greenville, SC, USA
| | - Katherine Downton
- Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA
| | - Emilie Ludeman
- Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA
| | - Virginia Noxon
- Department of Clinical Pharmacy and Outcomes Science, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA
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Abraham J. Introduction and Commentary: Paving the Way for Biosimilars in Oncology, Part 3. Semin Oncol 2014; 41 Suppl 3:S1-2. [DOI: 10.1053/j.seminoncol.2014.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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