Biotech Values

[DewDiligence]

HCV: Most Likely to Succeed (IMHO)

[Revised entry for VRTX’s VX-813/VX-985 as
noted in the second paragraph of #msg-42917596.]


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.

Please see #msg-42396728 for the distinction between a nucleoside and a nucleotide.


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-33270634.

Telaprevir in the second-line setting: phase-3 program (REALIZE study): #msg-32901932; phase-2 program: #msg-37316151 (PROVE-3 study), #msg-28749322 (‘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 (f/k/a/ R7128), the two oral drugs that Roche is testing in the INFORM-1 study that does not include interferon or ribavirin: #msg-42094151 (AASLD 2009 abstract); #msg-37309589 (PR re data at EASL 2009); #msg-36388140 (EASL 2009 abstract); #msg-37312942 (viral-load chart with annotations by ghmm); #msg-37208214 (PR on expanded trial design); #msg-37209844 (clinicaltrials.gov listing); #msg-36455893 (musings by tony111 and ghmm).

ITMN-191 (ITMN/Roche; phase-2b) is a protease inhibitor: #msg-40679281, #msg-40828534 (phase-2b design and musings); #msg-37306972, #msg-34747018 (phase-1b data); #msg-42016434 (boosting with ritonavir).

RG7128 (VRUS/Roche; phase-2b) is a nucleoside polymerase inhibitor: #msg-34746768.

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 (HGSI/NVS; BLA submission pending): #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 TMC435 (Medivir/JNJ; phase-2), a protease inhibitor: #msg-37298740; SCH 900518 (MRK, phase-2a), a protease inhibitor (follow-up to Boceprevir): #msg-34338549, #msg-34774813; GS9190 (GILD; phase-2), a non-nucleoside polymerase inhibitor that GILD is testing in an all-oral combination with GILD’s newly disclosed protease inhibitor GS9256: #msg-42717806; IDX184 (IDIX; phase-1b), a nucleotide polymerase-inhibitor: #msg-36392616 (EASL 2009 abstract), #msg-34763865 (PR for trial commencement), #msg-26915921 (how IDX184 is better than NM283); PSI-7851 (VRUS, phase-1b), a nucleotide polymerase inhibitor: #msg-40115833; IFN-alpha-XL (FLML; phase-1b): #msg-28837983; 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 (VCH-759 is a backup): #msg-37089807; IFN-Lambda (BMY/ZGEN; phase-1b): #msg-34768182 (BMY partnership), #msg-37277825 (interim phase-1b data); 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, entering phase-2), a non-nucleoside “palm” polymerase inhibitor that caused severe rash in phase-1 monotherapy (#msg-40064675).


5. Very-early-stage compounds that use an established MoA. These include ACH-1625 (ACHN;phase-1b), a protease inhibitor: #msg-41967587; IDX375 (IDIX, preclinical), a non-nucleoside “palm” polymerase inhibitor: #msg-34334563, #msg-31043481; 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; IDX136/IDX316 (IDIX, preclinical), two closely related macrocyclic protease inhibitors of which IDIX will select one to advance into phase-1: #msg-37246670 (EASL 2009 PR), #msg-37315636 (EASL 2009 poster); BMS-650032 (BMY, phase-1b), a protease/NS3 inhibitor: #msg-40361108; and VX-813/VX-985 (VRTX, phase-1/preclinical), protease inhibitors that are nominally the follow-ups to Telaprevir but are (IMO) close to being killed for lack of commercial relevance: #msg-42917596.


6. Agents in phase-2 or earlier that use a novel MoA. These include CF-102 (Can-Fite, phase-1/2), a polymerase inhibitor that purportedly induces apoptosis: #msg-39588570; BMS-790052 (BMY, phase-2), an NS5A inhibitor: #msg-40350075, #msg-33270670; MB11362 (Roche/MBRX, preclinical), MoA undisclosed: #msg-38456136; A-831 (AZN, status unknown), an NS5A inhibitor: #msg-16682361; a preclinical NS5A inhibitor from GSK (acquired from Genelabs): #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-42293996, #msg-38860625; and a preclinical entry inhibitor from PGNX: #msg-38519885.


7. Programs that are nominally alive but not receiving financial support. These include ANA773 (ANDS, phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; and 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). (VRX, under a different name, is the inventor of ribavirin.)


JMHO, FWIW