Snapshot: HCV Drugs in Development

It’s becoming a daunting task to follow the field given the rapid-fire release of study results and the many recent submissions of new direct-acting antiviral (DAA) drugs. All will be given as cocktails, with or without interferon or ribavirin, and for various durations depending on genotype (GT) and other factors.  How many permutations are possible, with 6 classes of drugs and several candidates to choose from in most classes?

Below an updated list of Phase 2 and 3 compounds; some soon to be approved by FDA. Several big pharma companies are rushing to catch up with Gilead, trying to participate in this high-stakes race to bring the first curative pan-genotypic once-a-day, short-duration treatment combo pill to the market.

Many similarities exist between the HIV and the HCV ‘world’ as far as the rapid progression of treatment generations are concerned.  The reign of IFN and ribavirin is almost over (nobody will miss them), short was the time on the market for the 1st generation protease inhibitors telaprevir and boceprevir. Nowadays, SVR rates of 90% have now become the norm for treatment-naive patients treated with sofosbuvir (Sovaldi) or simeprevir (Olysio) plus Peg-IFN/RBV.  A pure DAA regimen is clearly not far away. The group of ‘non-responders’ is getting smaller by the day.

With high SVR rates taken for granted, differentiation along the important secondary dimensions (safety, tolerability, drug interactions, convenient dosing, and health economics) will become critical success factors. Ultimately the winning team will be decided by the markets.

All of this is great news for patients who have been waiting long for DAAs. Even if the price tag is high at this stage, every new entry into the clinic will change the competitive landscape. With politicians already complaining about the exorbitant cost of Sovaldi, there will be pressure to break Gilead’s early lock on the market.

Treatment responses are not uniform across HCV subpopulations.   Hence, showing excellent efficacy in GT1 patients is just the start.  The new crop of HCV agents still have an open field for differentiation: in GT3, cirrhosis, pre- and post-transplant, and previous non-responder populations, just to name a few.  Not to forget the group of co-infected patients (both HIV and HBV) that would need dual viral therapies without PK/PD interference.  Note: not all drugs have uniform pan-genotypic activity.

CodenameDrug / GenericPI (NS3/4a)NS5aNS5b inh nucleosidicNS5b inh non-nukePhaseCompany
ABT-333Dasabuvirx3Abbvie
ABT-267Ombitasvir x3Abbvie
ABT-450/r x3Abbvie
ABT-072x2Abbvie
ACH-1625Sovaprevirx2Achillion
ACH-2684x2Achillion
ACH-3102x2Achillion
ACH-3422x1Achillion
BMS-650032Asunaprevirx3BMS
BMS-790052Daclatasvirx3BMS
BMS-791325x3BMS
BI-201335Faldaprevir x3Boehringer
GS-5885Ledipasvirx3Gilead
GS-5816x2Gilead
GS-9669x1Gilead
TMC-647055x2JNJ
JNJ-56914845x2GSK
MK-7009Vaniprevirx3Merck
MK-5172 x3Merck
MK-8742x3Merck
IDX-719Samatasvirx2Merck / Idenix
RG-7227Danoprevir/rx2Roche
RG-7128Mericitabinex2Roche
RG-7790Setrobuvirx2Roche
VX-135x2Vertex
PPI-668x2Presidio
GS-9451Vedroprevir2Gilead
DEB-025Alisporovir2Novartis

Status: 6/17/2014  –  only Phase 2 and later

Note: Tegobuvir/Gilead was discontinued.

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