New strategies for the treatment of hepatitis C virus infection and implications of resistance to new direct-acting antiviral agents

Figures & data

Table 1 Novel interferon (IFN) and ribavirin (RBV) preparations

	Class	Agent		Phase of development
	Type III IFN	IFN-λ1 (IL-29)		Phase IIb
IFN	Slow-release type I IFN	Albuferon	Zalbin (USA)	Under review
			Joulferon (EU)	Halted
		Locteron (BLX-883)		Phase II
	Oral IFN-α	Belerofon		Phase II1
RBV	RBV prodrug	TBV		Phase III

Note:

1 Phase II 2007.

Table 2 Some of the most promising direct-acting antiviral agents

Viral life cycle step	Target	Agent	Phase of development
Post-translational processing	NS3/4A protease	Telaprevir (VX-950)	Phase III1
		Boceprevir (SCH503034)	Phase III1
		GS-9256	Phase II
		BI 201335	Phase II
		RG7227 (Danoprevir)	Phase II
		Vaniprevir (MK-7009)	Phase II
		Narlaprevir (SCH900518)	Phase II
		TMC435	Phase IIa
		BMS-650032	Phase II
		BMS-791325	Phase II
		Danoprevir	Phase II
		ABT-450	Phase II
	NS3 helicase	BTN10/BTN11	Preclinical
Replication	NS5A	AZD-7295	Phase II
		BMS-790052	Phase II
		A-832	Phase II
	NS5B (NI)	RG-7128	Phase II
		PSI-7977	Phase II
		Tegobuvir	Phase II
		IDX184	Phase II
	NS5B (NNI)	GS-9190	Phase II
		ABT-333	Phase II
		ANA598	Phase II
		BI-207127	Phase II
		ABT-072	Phase II
		Filibuvir (PF-00868554)	Phase II
		VCH-916	Phase II
		VX-222	Phase II
		VX-759	Phase II

Note:

1 Putative final approval in 2011.

Figure 1 Hepatitis C virus life cycle and putative targets to design specific drugs.

Provided by courtesy of Dr Charles Rice and Dr Shihyun You.

Table 3 SOC-free DAA combinations

Agent 1	Agent 2	Phase of development
RG7227 (ITMN-191) (Danoprevir) (protease inhibitor)	RG7128 (polymerase inhibitor)	Phase I
BMS-650032 (protease inhibitor)	BMS-790052 (NS5A inhibitor)	Phase I
GS9256 (protease inhibitor)	Tegobuvir (polymerase inhibitor)	Phase II
Telaprevir (protease inhibitor)	VX-222 (polymerase inhibitor)	Phase II