Original article Rodriguez-Torres, M. et al. Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C. N. Engl. J. Med. 360, 257–267 (2009). PubMed
Sustained virological response (SVR) rates to therapy for HCV genotype 1 are lower in white Latino than in white non-Latino individuals, reported Dr Rodriguez-Torres and colleagues in their recent article in The New England Journal of Medicine. "Strategies to improve [SVRs] in Latinos are needed," the authors concluded.
Ethnicity is known to affect response to therapy in patients with HCV infection, but few relevant data are available. Latino individuals, in particular, are under-represented in clinical trials; HCV infection in this group is particularly aggressive and is associated with increased mortality.
This led Rodriguez-Torres and colleagues to investigate the effect of ethnicity on response to once-weekly treatment with peginterferon 2a (180 ;g/week) plus ribavirin (1 g or 1.2 g daily) in patients with HCV genotype 1. The researchers compared rates of response to therapy in white Latino individuals (n = 269) with those in the white non-Latino patients (n = 300). Only Latino individuals whose parents and grandparents spoke Spanish were eligible for inclusion in this prospective, multicenter, open-label, nonrandomized study. A significantly greater proportion of non-Latino than Latino patients (49% versus 34%) achieved an SVR. Furthermore, failure to detect serum HCV RNA at week 4 and throughout the treatment period occurred more frequently in non-Latino than in Latino patients. However, fewer Latino than non-Latino individuals withdrew from treatment owing to adverse events (9% versus 14%).
[Added entries for MK-3281, ITX5061, and cyclophilin inhibitors from NVS and Debiopharm.]
The following paragraphs are in descending order of likelihood of success. There is no claim of completeness here; i.e. paragraphs 3-6 do not necessarily mention all of the applicable drug candidates within the grouping. Please see #msg-36688204 for the semantics of the terms nucleoside and 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.
These two drugs have shown comparable efficacy in 24-28 week regimens of phase-2 trials in the genotype-1, treatment-naïve setting: #msg-31190433, #msg-33793333, #msg-33282976. Background posts: VRTX PROVE-1/2 trials made simple: #msg-29019931; PROVE-1/2 detailed results: #msg-28746843; overview of Telaprevir phase-3 program: #msg-27623529 (ADVANCE study), #msg-26228377 (outline of both studies); Boceprevir enrollment complete in phase-3 treatment-naïve trial (SPRINT-2): #msg-35116309; details of Boceprevir phase-3 program (SPRINT-2 and RESPOND-2): #msg-29474929.
Telaprevir and Boceprevir are also being tested in the second-line setting, Telaprevir in 24- and 48-week regimens and Boceprevir in 36- and 48-week regimens. Background posts: Telaprevir phase-3 REALIZE study: #msg-32901932; Telaprevir phase-2b PROVE-3 study: #msg-36464842; Telaprevir ‘107’ open-label phase-2 extension for PROVE-1/2 failures: #msg-33282976; Boceprevir phase-3 RESPOND-2 study: #msg-29474929.
2. ITMN-191 and R7128, the two oral drugs that Roche is testing is the INFORM-1 study that does not include interferon or ribavirin: #msg-36349693 (trial-design chart), #msg-33967428 (clinicaltrials.gov listing), #msg-33446127 (PR on study commencement), #msg-36388140 (EASL 2008 abstract), #msg-36455893 (musings by ghmm). ITMN-191 a.k.a. R7227 (ITMN/Roche; phase 1b) is a protease inhibitor: #msg-34747018. R7128 (VRUS/Roche; entering phase-2b) is a nucleoside polymerase inhibitor: #msg-34746768, #msg-35888562, #msg-32238916, #msg-32651030.
Although ITMN-191 and R7128 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. Agents in phase-2b, phase-3 or later that use an established MoA: Albuferon (HGSI/NVS; BLA submission pending): #msg-36140577 (phase-3 data), #msg-36254180 (lack of SPA!), #msg-34770426 (new trial with monthly dosing); BI201335 (B-I; phase-2b), a protease inhibitor: #msg-33564560, #msg-34774813; and Locteron (Biolex; phase-2), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-28786162. (Biolex recently bought out its partner, OctoPlus, and raised $60M to fund the Locteron program: #msg-32662307, #msg-32662762.)
4. Agents in phase-1 or phase-2a that use an established MoA. These include TMC435 (Medivir/JNJ; phase-2), a protease inhibitor: #msg-33283588, #msg-34774813; SCH 900518 (MRK, phase-2a), a protease inhibitor (follow-up to Boceprevir): #msg-34338549, #msg-34774813; GS-9190 (GILD; phase-2), a non-nucleoside polymerase inhibitor: #msg-32919311; IDX184 (IDIX; phase-1b), a nucleotide polymerase-inhibitor: #msg-36392616 (EASL 2008 abstract), #msg-34763865 (PR for trial commencement), #msg-26915921 (how IDX184 is better than NM283); PSI-7851 (VRUS, entering phase-1), a nucleotide polymerase inhibitor: #msg-36685948; ANA598 (ANDS, phase-1b), a non-nucleoside “palm” polymerase inhibitor: #msg-34678306; IFN-alpha-XL (FLML; phase-1b): #msg-28837983; ABT-450 (ABT/Enanta, phase-1), a protease inhibitor: #msg-35708745; VCH-222/VCH-759 (VRTX, phase-1b/2a), non-nucleoside “thumb” polymerase inhibitors that VRTX acquired from ViroChem: #msg-36022752, #msg-36023139; IFN-Lambda (BMY/ZGEN; phase-1b): #msg-34768182 (BMY partnership), #msg-33311734 (interim phase-1b data); and MK-7009 (MRK, phase-2a), a protease inhibitor that might bite the dust due to MRK’s acquisition of SGP: #msg-34337398, #msg-34335327.
5. Very-early-stage compounds that use an established MoA. These include ACH-1625 (ACHN; preclinical), a protease inhibitor: #msg-31459921; 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-36508769; ‘hyperglycosylated’ interferon (Alios BioPharma, preclinical): #msg-35612425; IDX136/IDX316 (IDIX, preclinical), two related macrocyclic protease inhibitors of which IDIX will select one to advance into phase-1: #msg-31043481; and VX-813/VX-985 (VRTX, phase-1/preclinical), protease inhibitors from VRTX being developed as follow-on compounds to Telaprevir: #msg-36022752.
6. Early- and very-early-stage compounds that use a novel MoA. These include BMS-790052 (BMY, phase-1), an NS5A inhibitor: #msg-33270670; A-831 (AZN, status unknown), an NS5A inhibitor: #msg-16682361; a preclinical NS5A program that GSK acquired from GNLB: #msg-33209281, #msg-33211420; ANA773 (ANDS, phase-1), an oral TLR7 modulator: #msg-33244419; IL-7 (Cytheris, phase-1/2) an injectable immunomodulator: #msg-33152073; NIM811 (NVS, status unknown) and Debio 025 (Debiopharm, phase-2), cyclophilin inhibitors: #msg-36507550; GI-5005 (GlobeImmune, phase-2), an injectable immunomodulator: #msg-33322543; ACH-1095 (ACHN/GILD; preclinical), an NS4A inhibitor: #msg-31459921; 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-31857987; nitazoxanide (Romark/Chugai, phase-2): #msg-35738696; and ITX5061 (iTherX, phase-2a), MoA unknown: #msg-35319690.
Market Data 
Markets 
AI
