Specifically targeted antiviral therapy for hepatitis C virus

Table 1 Anti-HCV agents currently under clinical development

Compound		Clinical advancement nt	Viral efficacy	Resistance (HCV resistant variants)	Remarks
Protease inhibitors	Telaprevir	II	(dose-750 mg q8h; genotype-1)	Low level: V36A/M, T54A, R155K/T, A156S	Rash, GI and hematological adverse events (AE)
	(VX-950)	PROVE- 1, 2, 3	VLR = 3 log d 3	High level: A156V/T, V36A/M-R155K/T, V36A/M-A156V/T;
			VLR = 4.4 log: d 14	After 14 d of treatment
			VLR = 5.5 log: d 14 when combined with PEG-IFNa2a
	SCH 503034	II	(dose 400 mg q8h; genotype-1)	Low to moderate levels:	Frequency of AE comparable to control group receiving placebo
			VLR = 2.06 log d 14	V170A
			VLR = 2.9 log: when combined with PEG-IFN	T54A
				A156S
				High level: A156T
Inhibitor of protease cofactor NS4A	ACH-806	I/II	VLR = 1 log: d 5	Single mutation at N-terminus of NS3; lack of cross resistance to any of the polymerase inhibitors or protease inhibitors now under development	Reversible nephrotoxicity
Polymerase inhibitors	Valopicitabine (NM283)	II	VLR = 0.8 log: d 28	S282T	GI and hematological AE
			VLR = 2.7 log: d 28, when combined with PEG-IFN
			VLR = 4.24 log: wk 24, when combined with PEG-IFN
	R1479 (R1626)	II	VLR = 3.7 log for 4500 mg q12h at d 14, VLR = 2.6 log for 3000 mg q12h	no data	Mild to moderate hematological AE with increasing doses
	HCV-796	II	VLR = 1.4-1.5 log: d 4	C316Y	Mild to moderate headache-the most frequent AE; no treatment-emergent serious AE
			VLR = 3.3-3.5 log: d 14, when combined with PEG-IFN
	BILB 1941	I	Data incomplete due to high discontinuation rate	No data	GI AE
Cyclophilin inhibitors	DEBIO 025	I	VLR = 3.6 log: d 14 of monotherapy	No breakthrough during the treatment	Transitional hyperbilirubinemia