Advances in hepatitis C therapy: What is the current state - what come’s next?

Table 1 Current recommendations of antiviral regimens depending on the genotype

DAA-regime	HCV-genotype
	1a	1b	2	3	4	5	6
SOF + R	(×)	(×)	×	×	(×)	(×)	(×)
SOF + SMV ± R	×	×			×
SOF + DCV1± R	×	×	(×)	×	×
SOF + LDV ± R	×	×		(×)	×	×	×
OBV + PTV/r ± DSV ± R (3D)	×	×
OBV + PTV/r ± R (2D)					×

¹DCV, no approval in the United States. DAA: Direct antiviral agents; LDV: Ledipasvir; SMV: Simeprevir; DCV: Daclatasvir; SOF: Sofosbuvir; OBV: Ombitasvir; PTV: Paritaprevir; HCV: Hepatitis C virus; DSV: Dasabuvir; R: Ribavirin; r: Ritonavir.

Table 2 Overview on clinical studies using the NS5B inhibitor sofosbovir

Study	Patient population	Therapy	Duration (wk)	SVR	Comments
ION-1	First-line therapy	SOF + LDV	12	99%
		SOF + LDV + R	12	97%
		SOF + LDV	24	98%
		SOF + LDV + R	24	99%
ION-2	Re-therapy	SOF + LDV	12	94%	86% cirrhotic
		SOF + LDV + R	12	96%	82% cirrhotic
		SOF + LDV	24	99%	100% cirrhotic
		SOF + LDV + R	24	99%	86% cirrhotic
ION-3	First-line therapy	SOF + LDV	8	94%	Only non-cirrhotic
		SOF + LDV + R	8	93%	Only non-cirrhotic
		SOF + LDV	12	95%	Only non-cirrhotic

SOF: Sofosbuvir; LDV: Ledipasvir; R: Ribavirin; SVR: Sustained virological response.

Table 3 Overview on clinical studies using the combination of paritaprevir/ritonavir + ombitasvir ± dasabuvir

Study	Patient population	Therapy	Duration (wk)	SVR	Comments
SAPPHIRE-I	First-line therapy	OBV + PTV/r + DSV + R	12	96%	No cirrhosis
SAPPHIRE-II	Re-therapy	OBV + PTV/r + DSV + R	12	96%	No cirrhosis
TURQUOISE-II	Cirrhosis	OBV + PTV/r + DSV + R	12	92%	GT1a 89%
					GT1b 99%
		OBV + PTV/r + DSV + R	24	96%	GT1a 95%
					GT1b 100%
PEARL-II	Re-therapy, GT1b	OBV + PTV/r + DSV	12	100%	No cirrhosis
		OBV + PTV/r + DSV + R	12	97%	No cirrhosis
PEARL-III	First-line therapy, GT1b	OBV + PTV/r + DSV	12	99%	No cirrhosis
		OBV + PTV/r + DSV + R	12	99%	No cirrhosis
PEARL-IV	First-line therapy, GT1a	OBV + PTV/r + DSV	12	90%	No cirrhosis
		OBV + PTV/r + DSV + R	12	97%	No cirrhosis

OBV: Ombitasvir; PTV: Paritaprevir; DSV: Dasabuvir; R: Ribavirin; r: Ritonavir; SVR: Sustained virological response.

Table 4 Overview on clinical studies using future antiviral drugs and combinations

Substances (study)	RBV	Genotype	Population	Duration (wk)	Phase	Results (SVR)
SOF + GS-5816 (NS5A)[47]	±	1	TN, NCi	8	II	81% - R; 90% + R; (n = 60)
	±	2	TN, NCi	8	II	88% - R; 88% + R; (n = 52)
	±	3	TN, NCi	8	II	96% - R; 100% + R; (n = 53)
	±	1	TE, Ci, NCi	12	II	NCi: 100% (n = 38); Ci: 100% - R, 90% + R (n = 17)
	±	3	TE, Ci, NCi	12	II	NCi: 100% (n = 53); Ci: 88% - R, 96% + R (n = 52)
SOF + ACH-3102 (NS5A) (PROXY)[48]	-	1	TN, NCi	6 and 8	II	100% after 6 wk (n = 12) or 8 wk (n = 12)
SOF/LDV + Vedroprevir (SYNERGY)[49]	-	1	TN, NCi	6	II	95% (n = 20)
SOF/LDV + GS 9669 (non-NUC-NS5B) (SYNERGY)[49]	-	1	TN, NCi	6	II	95% (n = 20)
SOF + Grazoprevir + Elbasvir (C-SWIFT)[46]	-	1, 3	TN, NCi	4 or 6 (GT1)	II	SVR8: GT1: 39% after 4 wk (n = 31); 87% after 6 wk (n = 30)
				8 or 12 (GT3)		GT3: 100% after 8 and 12 wk (n = 15/14)
			TN, Ci	6 or 8 (GT1)	II	SVR8: GT1: 80% after 6 wk (n = 20); 89% after 8 wk (n = 21)
				12 (GT3)		GT3: 90% (n = 12)
Grazoprevir + Elbasvir	±	1	TN, NCi	8 or 12	II	8 wk GT1a: 80%
(C-WORTHY)[50]						12 wk: 98% - R; 93% + R
			TN, Ci	12 or 18	II	12 wk: 97% - R; 90% + R
						18 wk: 94% - R; 97% + R
			TE, Ci, NCi	12 or 18	II	12 wk: 91% - R; 94% + R
						18 wk: 97% - R; 100% + R
SMV + Samatasvir (HELIX-1)[51]	+	1b, 4	TN, NCi	12	II	SVR4: GT1b: 80% (n = 84)
						GT4: 100% (n = 9)
Asunaprevir + DCV + Beclabuvir (UNITY 1)[52]	-	1	TN, TE, NCi	12	III	TN: 91%; TE: 89%
Asunaprevir + DCV + Beclabuvir (UNITY 2)[53]	±	1	TN, TE, Ci	12	III	90% - R; 96% + R

TN: Therapy-naive; TE: Therapy-experienced; Ci: Cirrhosis; NCi: No cirrhosis; GT: Hepatitis C virus-genotype; SOF: Sofosbuvir; LDV: Ledipasvir; R: Ribavirin; SVR: Sustained virological response; SMV: Simeprevir; DCV: Daclatasvir.