Scientists are getting closer to finding the killer app in treating hepatitis C, but it may be too soon to pick a winner.

Bristol-Myers Squibb and Gilead say that an all-oral therapy joining daclatasvir from BMS and Gilead's GS-7977 suppressed the virus in more than 95% of patients across a broad spectrum of genotypes.

The two drugs reached a 100% sustained virologic response (SVR), or cure rate, at week four in a common subgroup, genotype 1 patients not previously treated with interferon.

The 100% rate held when ribavirin, another traditional treatment mainstay, was not in the mix, bettering the roughly 90% SVR rate seen in trials for an Abbott triple therapy.

The direct-acting antivirals (DAAs) from BMS, Gilead and Abbott showed the best efficacy and tolerability of those presented at the European Association of the Study of Liver Disease (EASL) in April.

The findings accelerated momentum in a fast-moving category. Not that there haven't been speed bumps. In February, Gilead's ‘7977 came under assault when data showed that six out of six subjects treated with the pipeline drug, all prior “null” responders to an interferon-containing regimen, experienced viral relapse within four weeks of completing an all-oral regimen of ‘7977 and ribavirin. Gilead's stock fell after the news.

Several analysts now believe daclatasvir, an NS5a inhibitor, and ‘7977, a nucleotide analog (or “Nuc”), may form the best treatment “backbone” option across all genotypes.
“The ‘killer app' in HCV is probably an NS5a plus a nuc without ribavirin,” ISI analyst Mark Schoenebaum declared.

The newer protease inhibitors—Vertex's Incivek and Merck's Victrelis—appear vulnerable to the all-oral regimens, but not for a few years.

“These results obviously reinforce the expectation that DAA-only (IFN and RBV-sparing) regimens will likely quickly supplant current HCV treatments when they become available in the 2015/2016 timeframe,” wrote Deutsche Bank's Barbara Ryan in a note.

In a dispatch to investors, Credit Suisse's Catherine Arnold said the data “takes a little shine off” Abbott's HCV program, “but we still view it as a competitive presence.” The triple therapy combines the firm's protease inhibitor ABT-450 + NS5B inhibitor ABT-333 + ribavirin. Another three-drug regimen including NS5B inhibitor ABT-072 also showed a high HCV cure rate.
The Gilead/BMS combo “represents the most compelling all-oral, interferon-free data in the highly visible [HCV] marketplace,” noted Arnold.

Gilead has many HCV compounds to pair its nuc with, including an NS5a like daclatasvir. That makes a Gilead-BMS partnership far from a given.

Ryan also cautioned that other factors—side effects, dosing convenience and cost—“will be important considerations in determining market share.”

Results from a mix of Gilead's ‘7977 and ribavirin hit an SVR rate of 88%—above the 50% the Street had expected, according to Schoenebaum. Abbott's all-oral triple combo may be another good backbone option, while daclatasvir looks like a solid add-on option and BMS is exploring multiple pairing options.

Other nucs in development include Vertex's ALS-2200 and ALS-2158, and biotech firm Idenix's IDX184, which can be combined with its NS5a inhibitor, IDX719.