Its no where near as up-to-date as Dew's Most Likely to Succeed but it does have pretty colors, links and a development chart. http://hcvdrugs.com/ Maybe if enough people e-mail them they'll update the site. Maybe DD can license out his HCV: MLtS list :-).
[Updated entries for GILD’s GS9190 and Conatus Pharma’s CTS-1027; new entry for ACHN’s ACH-2684.]
The following paragraphs are in descending order of likelihood of success. There is no claim of completeness here; i.e. paragraphs 3-7 do not necessarily mention all of the applicable drug candidates within the grouping. (Within each numbered paragraph 3-7, the order of the listed entries is not intended to convey any meaning.)
Please see #msg-42396728 for the distinction between a nucleoside and a nucleotide, and see #msg-43114117 for some historical perspective from the HIV arena.
1. The two leading protease inhibitors: Telaprevir (VRTX/JNJ; phase-3) and Boceprevir (MRK; phase-3). The Telaprevir program is further advanced, so let’s call Telaprevir and Boceprevir 1a and 1b, respectively. Both drugs have shown very impressive efficacy in phase-2 trials, although neither has a completely clean safety profile (see references below).
Telaprevir in the treatment-naïve setting: phase-3 program: #msg-27623529 (ADVANCE study), #msg-26228377 (both studies); phase-2b program: #msg-29019931 (PROVE-1/2 trials made simple), #msg-28746843 (PROVE-1/2 detailed results); C208 study of BID vs TID dosing: #msg-43114192.
Telaprevir in the second-line setting: phase-3 program (REALIZE study): #msg-32901932; phase-2 program: #msg-37316151 (PROVE-3 study), #msg-42965441 (‘107’ open-label extension for PROVE-1/2 failures).
Boceprevir in the treatment-naïve setting: phase-3 program (SPRINT-2 and RESPOND-2): #msg-29474929; phase-2b program: #msg-42086185 (AASLD 2009 abstract re SPRINT-1), #msg-37298987, (interim SPRINT-1 results at EASL 2009), #msg-37298085 (EPO usage), #msg-31190433 (Dew’s musings on SPRINT-1 data).
Boceprevir in the second-line setting: phase-3 (RESPOND-2) study: #msg-29474929.
2. ITMN-191 (a/k/a/ RG7227) and RG7128, the two oral drugs that Roche is testing in the INFORM-1 study that does not include interferon or ribavirin: #msg-43185247 (AASLD 2009), #msg-37309589 (EASL 2009), #msg-37312942 (viral-load chart from EASL 2009 with annotations by ghmm), #msg-37208214 (Apr 2009 PR on expanded trial design), #msg-37209844 (clinicaltrials.gov listing).
Although ITMN-191 and RG7128 are not necessarily the best drugs in their respective classes, the fact that Roche is testing them in INFORM-1 gives them a leg up on competing drugs at the same stage of development, IMO.
3. Other agents in phase-2b or later: Albuferon/Zalbin/Joulferon (HGSI/NVS; BLA and MAA submitted): #msg-36140577 (phase-3 data), #msg-36254180 (lack of SPA!), #msg-34770426 (new trial with monthly dosing); BI 201335 (B-I; phase-2b), a protease inhibitor: #msg-42086185, #msg-33564560; and Locteron (Biolex; phase-2b), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-37298340 (phase-2a data from EASL 2009), #msg-37178496 (phase-2b design), #msg-40953698 (manufacturing agreement).
4. Agents in phase-1b or phase-2a that use an established MoA. These include ACH-1625 (ACHN;phase-1b), a protease inhibitor: #msg-45339022, #msg-44560695, #msg-44566075; BMS-650032 (BMY, phase-2), a protease/NS3 inhibitor that’s being tested in an all-oral phase-2 trial with BMS-790052 (see paragraph 6 below): #msg-44700187, #msg-40361108; TMC435 f/k/a/ TMC435350 (Medivir/JNJ; phase-2b), a protease inhibitor: #msg-43361309 (overview of phase-2a/2b program at 2009 AASLD), #msg-37298740 (phase-2a data at EASL 2009), #msg-45415884 (2010 PK trial re hepatic impairment); SCH 900518 a/k/a/ Narlaprevir (MRK; phase-2a), a protease inhibitor: #msg-43169835 (interim phase-2a data), #msg-34338549 (final phase-1b data); GS9190 (GILD; phase-2), a non-nucleoside polymerase inhibitor with QT-prolongation issues that GILD is testing in an all-oral combination with GILD’s newly disclosed protease inhibitor GS9256: #msg-46036072; IDX184 (IDIX; phase-2), a nucleotide polymerase-inhibitor: #msg-45350536 (first phase-2 combo data), #msg-39719159, #msg-39720566 (phase-1b monotherapy data), #msg-26915921 (how IDX184 is better than NM283); PSI-7977 (VRUS, phase-2a), a nucleotide polymerase inhibitor that’s a single-isomer version of PSI-7851: #msg-45735193 (start of phase-2a), #msg-40115833 (phase-1b data for PSI-7851); IFN-alpha-XL (FLML; phase-2a): #msg-44688995; ABT-450 (ABT/Enanta, phase-1), a protease inhibitor: #msg-35708745; VCH-222 (VRTX, phase-1b), a non-nucleoside “thumb” polymerase inhibitors that VRTX acquired from ViroChem: #msg-45333756, #msg-37089807; IFN-Lambda (BMY/ZGEN; phase-2): #msg-34768182 (BMY partnership), #msg-43123220 (final phase-1b data), #msg-43360640 (start of phase-2); MK-7009 (MRK, phase-2a), a protease inhibitor: #msg-34337398, #msg-34335327; ABT-333 (ABT, phase-1b), a polymerase inhibitor: #msg-42098204; and ANA598 (ANDS, phase-2), a non-nucleoside “palm” polymerase inhibitor: #msg-44635086 (interim phase-2 PR), #msg-44647384 (interim tabular data), #msg-44645147 (musings on interim data), #msg-40064675 (musings on phase-1b data).
5. Very-early-stage compounds that use an established MoA. These include IDX320 (IDIX, phase-1), a macrocyclic protease inhibitor: #msg-45598790); IDX375 (IDIX,phase-1), a non-nucleoside “palm” polymerase inhibitor: #msg-45350536; MK-3281 (MRK, phase-1), a non-nucleoside “thumb” polymerase inhibitor: #msg-42093301 (safety signal in AASLD 2009 abstract); PSI-938 and PSI-879 (VRUS, preclinical), a pair of purine-analog nucleotide prodrugs: #msg-39322313, #msg-42245955; ‘hyperglycosylated’ interferon (Alios BioPharma, preclinical): #msg-35612425; ACH-2684 (ACHN, preclinical), a (presumed) NS3/helicase/protease inhibitor: #msg-46027189.
6. Agents in phase-2 or earlier that use a novel MoA. These include BMS-790052 (BMY, phase-2), an NS5A inhibitor that’s being tested in an all-oral phase-2 trial with BMS-650032 (see paragraph 4 above): #msg-44700187, #msg-33270670; CTI-1027 (Conatus, phase-2): #msg-46034554; CF-102 (Can-Fite, phase-1/2), a polymerase inhibitor that purportedly induces apoptosis: #msg-39588570; MB11362 (Roche/MBRX, preclinical), MoA undisclosed: #msg-38456136; A-831 (AZN, status unknown), an NS5A inhibitor: #msg-16682361; an unnamed NS5A inhibitor that GSK acquired from Genelabs (status unknown): #msg-33209281, #msg-33211420; IL-7 (Cytheris, phase-1/2) an injectable immunomodulator: #msg-33152073; Debio 025 (Debiopharm, phase-2a), a cyclophilin inhibitor: #msg-37359213; NIM811 (NVS, status unknown), a cyclophilin inhibitor: #msg-36507550; GI-5005 (GlobeImmune, phase-2), an injectable immunomodulator: #msg-37298510; ACH-1095 (ACHN, preclinical), an NS4A inhibitor that GILD dropped while retaining the right to opt back in: #msg-41217537; an unnamed NS5A inhibitor that VRTX acquired from ViroChem (preclinical): #msg-36022752; an unnamed NS5A inhibitor from Presidio Pharma (status unknown): #msg-27791536; clemizole (Stanford University, preclinical), an NS4B inhibitor: #msg-39883747; nitazoxanide (Romark/Chugai, phase-2): #msg-35738696; ITX5061 (iTherX, phase-2a), MoA unknown: #msg-35319690; IMO-2125 (IDRA, phase-1), a TLR9 agonist: #msg-44746537; SD-101 (DVAX, phase-1b), a TLR9 agonist: #msg-45932364; a preclinical entry inhibitor from PGNX: #msg-38519885; SPC3649 (Santaris, preclinical), MoA based on microRNA: #msg-44177354.
7. Programs that are nominally alive but are not active. These include ANA773 (ANDS, phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; taribavirin (VRX, phase-2b), a “legacy” prodrug of ribavirin that has been floating around for a long time: #msg-38280961 (musings on final phase-2b data), #msg-37299101 (detailed 60-week data); and VX-813/VX-985 (VRTX, phase-1/preclinical), protease inhibitors that were previously touted as the backups to Telaprevir: #msg-45333927.
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