Merck's hepatitis C cocktail drug fails

After sendin for its hepatitis C regimen, Merck investigators hailed the clear success of an 8-week test but confirmed analysts' fears in a batch of 4-week data released at the meeting of the American Association for the Study of Liver Diseases.

A mix of grazoprevir/elbasvir (MK-5172/MK-8g out signals that it might be running into trouble with a short-duration study of a new triple combination drug742, MK-5172A)--the company's investigational NS3/4A protease inhibitor and NS5A inhibitor, in combination with Gilead's Sovaldi (sofosbuvir), an NS5B nuc inhibitor, clearly hit the mark with a 94.7% cure rate for treatment naïve cirrhotic patients at 8 weeks. But the combination fell well short of the goal line on efficacy at 4 weeks, with a cure rate of 38.7%. At 6 weeks the triple hit an 80% cure rate in the treatment-naïve group of cirrhotic patients while the non-cirrhotic cohort hit 86.7%--shy of the 90% level some analysts believe Merck is likely to face as a competitive hurdle cleared by rivals. All the patients in the study were genotype 1.

Merck's team declared the numbers were a win, but several analysts concluded that Gilead is the real winner today. In premarket trading Monday, Gilead's shares jumped more than 2% as the market potential for Merck's rival approach faded somewhat. The focus at Merck, which saw its shares slip about 2% this morning, will now be on new studies that include a new hep C drug--MK-3682--recently added to its portfolio.

Merck's next step will be to cut loose from Sovaldi and get its own MK-3682--acquired in the $3.85 billion Idenix buyout--into a slate of Phase II studies that will look at 8-week results. And Merck says it may once again go even shorter than that. At this point, a variety of new therapies are coming along that will likely eliminate the virus--the rivalry now centers on just how fast it can be done reliably.

Dupilumab emerged from Regeneron's development platform, which has also produced a closely-watched PCSK9 cholesterol drug that is also partnered with Sanofi. While the pharma giant has struggled to develop new drugs--recently bidding its CEO Chris Viehbacher goodbye after an internal squabble with the board--its partnership with Regeneron has produced most of its most promising late-stage drugs.

A win here would be big for Regeneron and huge for Sanofi. Leerink Swann analyst Joseph Schwartz has projected peak annual sales potential for dupilumab at $2.8 billion for two indications--asthma and atopic dermatitis indication. And the partners could be setting the stage for even more.

Regeneron and Sanofi face some competition which is even further advanced in the clinic. Just days ago GlaxoSmithKline filed for an approval of its IL-5 asthma drug mepolizumab, with Teva (reslizumab) and AstraZeneca (benralizumab) trailing along the IL-5 pathway. AstraZeneca has posted a peak sales estimate for its drug--which has had mixed results in mid-stage trials--at $2 billion. And they all expect that their drugs can also hit the mark for COPD.