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Schaefer R, Ayvaz A, Hoffman CR, Yann M, Rooney Z, Leus M, Mitra S, Miller V. Twenty-five years of addressing cutting-edge scientific, policy, and regulatory issues through collaboration: The Forum for Collaborative Research. Clin Transl Sci 2024; 17:e70051. [PMID: 39425910 PMCID: PMC11490216 DOI: 10.1111/cts.70051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 09/27/2024] [Accepted: 10/03/2024] [Indexed: 10/21/2024] Open
Abstract
Developing safe and effective drugs and other medical products is a complex and costly process. Drug development has been, historically, commonly competitive and uncollaborative, and this tendency toward a lack of interaction between stakeholders-the pharmaceutical industry, academia, regulatory agencies, healthcare providers, and communities, among others-can lead to missed opportunities to improve efficiency and, ultimately, public health. The Forum for Collaborative Research was established in 1997 to address current scientific, policy, and regulatory issues in global health through multistakeholder engagement and dialogue. By providing a neutral and safe space for discussion, the Forum's model has impacted how clinical trials in diverse health areas are conducted, supported broader and more equitable clinical trial participation, and accelerated delivery of new drugs. The Forum's focus and directions have shifted over time, and this responsiveness to the needs of the global health community will be critical to ensure that the Forum continues to support collaboration in global health. In this article, we present lessons learned from this innovative model of collaborative research and regulatory science, pioneered by the Forum for over 25 years, including the importance of collective ownership and governance by all stakeholders, and emphasis on common goals and advantages of collaboration.
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Affiliation(s)
- Robin Schaefer
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
| | - Alessi Ayvaz
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
| | - Christopher R Hoffman
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
| | - Margot Yann
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
| | - Zachary Rooney
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
| | - Mitchell Leus
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
| | - Shilpa Mitra
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
| | - Veronica Miller
- Forum for Collaborative Research, University of California, Berkeley, Washington, DC, USA
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Wallace J, Richmond J, Howell J, Hajarizadeh B, Power J, Treloar C, Revill PA, Cowie B, Wang S, Stoové M, Pedrana A, Hellard M. Exploring the Public Health and Social Implications of Future Curative Hepatitis B Interventions. Viruses 2022; 14:2542. [PMID: 36423153 PMCID: PMC9693003 DOI: 10.3390/v14112542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 11/11/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Hepatitis B is a significant global health issue where the 296 million people estimated to live with the infection risk liver disease or cancer without clinical intervention. The World Health Organization has committed to eliminating viral hepatitis as a public health threat by 2030, with future curative hepatitis B interventions potentially revolutionizing public health responses to hepatitis B, and being essential for viral hepatitis elimination. Understanding the social and public health implications of any cure is imperative for its successful implementation. This exploratory research, using semi-structured qualitative interviews with a broad range of professional stakeholders identifies the public health elements needed to ensure that a hepatitis B cure can be accessed by all people with hepatitis B. Issues highlighted by the experience of hepatitis C cure access include preparatory work to reorientate policy settings, develop resourcing options, and the appropriateness of health service delivery models. While the form and complexity of curative hepatitis B interventions are to be determined, addressing current disparities in cascade of care figures is imperative with implementation models needing to respond to the cultural contexts, social implications, and health needs of people with hepatitis B, with cure endpoints and discourse being contested.
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Affiliation(s)
- Jack Wallace
- Burnet Institute, Melbourne, VIC 3004, Australia
- Australian Research Centre in Sex, Health and Society, Latrobe University, Bundoora, VIC 3083, Australia
- Centre for Social Research in Health, UNSW, Sydney, NSW 2052, Australia
| | | | - Jessica Howell
- Burnet Institute, Melbourne, VIC 3004, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia
- Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia
| | | | - Jennifer Power
- Australian Research Centre in Sex, Health and Society, Latrobe University, Bundoora, VIC 3083, Australia
| | - Carla Treloar
- Centre for Social Research in Health, UNSW, Sydney, NSW 2052, Australia
| | - Peter A. Revill
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia
- Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia
| | - Benjamin Cowie
- WHO Collaborating Centre for Viral Hepatitis, Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia
| | - Su Wang
- Center for Asian Health, Saint Barnabas Medical Center, RWJBarnabas-Rutgers Medical Group, Florham Park, NJ 07039, USA
| | - Mark Stoové
- Burnet Institute, Melbourne, VIC 3004, Australia
| | | | - Margaret Hellard
- Burnet Institute, Melbourne, VIC 3004, Australia
- Department of Infectious Diseases, Alfred Health & Monash University, Melbourne, VIC 3004, Australia
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Luk A, Jiang Q, Glavini K, Triyatni M, Zhao N, Racek T, Zhu Y, Grippo JF. A Single and Multiple Ascending Dose Study of Toll-Like Receptor 7 Agonist (RO7020531) in Chinese Healthy Volunteers. Clin Transl Sci 2020; 13:985-993. [PMID: 32268000 PMCID: PMC7485962 DOI: 10.1111/cts.12791] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 03/08/2020] [Indexed: 02/06/2023] Open
Abstract
Toll‐like receptor 7 (TLR7) agonists modulate broad spectrum immune activity and are evaluated in the treatment of human diseases, including cancer and chronic viral infection. RO7020531, an oral prodrug of a TLR7 agonist, is in clinical development as part of a curative regimen against chronic hepatitis B. We report the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of RO7020531 in healthy Chinese volunteers following single and multiple ascending doses (SAD and MAD). PK and PD samples were evaluated from four SAD cohorts and 3 MAD cohorts with 10 subjects each (8 active and 2 placebo). Safety and tolerability were monitored throughout the study. A total of 155 adverse events (AEs) were reported in 49 subjects. Fifty‐one AEs in 18 subjects were assessed as treatment‐related. Most of the AEs were mild; nine subjects experienced moderate AEs; there were no severe AEs. In two 150 mg MAD cohorts given every other day (q.o.d.), 7 of 20 subjects experienced pyrexia and were discontinued due to transient asymptomatic lymphopenia, which resolved 24–48 hours postdose. The PK of the active metabolite, RO7011785, increased linearly with dose from 40 mg to 170 mg. There was no PK accumulation following q.o.d. dosing. The PK profile is consistent with observations in white subjects in the global first‐in‐human study. SADs and MADs of RO7020531 resulted in dose‐dependent increases in TLR7 response markers at 100 mg or above. Flu‐like symptoms were associated with higher interferon‐α levels. RO7020531 was safe and acceptably tolerated in healthy Chinese volunteers with a multiple 150 mg q.o.d. dose regimen.
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Affiliation(s)
- Andrea Luk
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Qiudi Jiang
- Roche Innovation Center Shanghai, Shanghai, China
| | | | | | - Na Zhao
- Roche Pharma Development Shanghai, Shanghai, China
| | - Tomas Racek
- Roche Innovation Center Basel, Basel, Switzerland
| | - Yonghong Zhu
- Roche Innovation Center Shanghai, Shanghai, China
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Editorial: Strategies and barriers for hepatitis B cure: implications for HIV. Curr Opin HIV AIDS 2020; 15:151-156. [PMID: 32229770 DOI: 10.1097/coh.0000000000000620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Samunuri R, Jha AK, Bal C. Rhodium catalyzed stereospecific reductive carbocyclization of 1,6-enynes and synthesis of 4'-methyl-6'-substituted aristeromycins. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS 2019; 38:391-399. [PMID: 30689527 DOI: 10.1080/15257770.2018.1554221] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The need of long-term treatment for chronic HBV, emergence of drug-resistant viruses and inefficiency of currently approved therapies to eliminate covalently closed circular DNA (cccDNA), mandates identification of potent and selective inhibitors of HBV replication with novel mechanisms of action. Entecavir, a carbocyclic guanosine nucleoside analog, is the most potent inhibitor of HBV replication on the market. Moreover, the naturally occurring carbocyclic nucleosides aristeromycin are known for their wide range of antiviral activities. In this research, we have utilized BINAP directed rhodium catalyzed reductive carbocyclization of 1,6-enynes (8a-b) through asymmetric hydrogenation which is an approach, not yet explored in carbocyclic sugar synthesis. Interestingly, we obtained exclusive anti-(9a) and Z-anti (9b) carbocyclic sugars. The new aristeromycin analogs (10a-b) with scaffold combination of entecavir and aristeromycin were then synthesized using the Mitsunobu reaction followed by deprotection.
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Affiliation(s)
- Ramakrishnamraju Samunuri
- a Chemistry Services , GVK Biosciences Pvt.Ltd , Hyderabad , Telangana , India.,b Department of Chemistry , Birla Institute of Technology , Ranchi , Jharkhand , India
| | - Ashok Kumar Jha
- a Chemistry Services , GVK Biosciences Pvt.Ltd , Hyderabad , Telangana , India
| | - Chandralata Bal
- b Department of Chemistry , Birla Institute of Technology , Ranchi , Jharkhand , India
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Bakacs T, Safadi R, Kovesdi I. Post-infection viral superinfection technology could treat HBV and HCV patients with unmet needs. HEPATOLOGY, MEDICINE AND POLICY 2018; 3:2. [PMID: 30288325 PMCID: PMC5918728 DOI: 10.1186/s41124-017-0028-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 12/19/2017] [Indexed: 02/07/2023]
Abstract
Background Viral hepatitis deaths from acute infection, cirrhosis, and liver cancer have risen from the tenth to the seventh leading cause of death worldwide between 1990 and 2013. Even in the oral direct acting antiviral (DAA) agent era there are still large numbers of patients with unmet needs. Medications approved for treatment of chronic hepatitis B virus (HBV) infection do not eradicate HBV often requiring treatment for life associated with risks of adverse reactions, drug resistance, nonadherence, and increased cost. Although DAAs increased virologic cure rates well over 90% in all hepatitis C virus (HCV) genotypes, HCV infection still cannot be cured in a small but significant minority of patients. While most of the medical issues of HCV treatment have been solved, the current costs of DAAs are prohibitive. Results The post-infection viral superinfection treatment (SIT) platform technology has been clinically proven to be safe and effective to resolve acute and persistent viral infections in 42 HBV and HCV patients (20 HBV, 22 HCV), and in 4 decompensated patients (2 HBV, 2 HCV). SIT employs a non-pathogenic avian double stranded RNA (dsRNA) virus, a potent activator of antiviral gene responses. Unexpectedly, SIT is active against unrelated DNA (HBV) and RNA (HCV) viruses. SIT does not require lifelong therapy, which is a major advantage considering present HBV treatments. The new viral drug candidate (R903/78) is homogeneously produced by reverse genetics in Vero cells. R903/78 has exceptional pH and temperature stability and also excellent long-term stability; therefore, it can be orally administered, stored and shipped without freezing. Since R903/78 is easy to stockpile, the post-infection SIT could also alleviate the logistic hurdles of surge capacity in vaccine production during viral pandemics. Conclusion To help large number of HBV and HCV patients with unmet needs, broad-spectrum antiviral drugs effective against whole classes of viruses are urgently needed. The innovative SIT technological platform will be a great additional armament to conquer viral hepatitis, which is still a major cause of death and disability worldwide.
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Affiliation(s)
| | - Rifaat Safadi
- 2Hadassah Hebrew University Medical Center, Jerusalem, Israel
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