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.
|Codename||Drug / Generic||PI (NS3/4a)||NS5a||NS5b inh nucleosidic||NS5b inh non-nuke||Phase||Company|
|IDX-719||Samatasvir||x||2||Merck / Idenix|
Status: 6/17/2014 – only Phase 2 and later
Note: Tegobuvir/Gilead was discontinued.