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Medivir, Gilead Oral Drug Pair Strong in HCV, Early Phase IIa

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By Randy Osborne
Staff Writer

Their oral combo drug's 100 percent success rate in hepatitis C virus (HCV) patients with liver fibrosis did not do much for shares of Medivir AB and partner Gilead Sciences Inc., probably because the positive interim results from the Phase IIa trial were "baked in" by investors, who must wait to find out more.

"It's in line with our expectations," said Decision Resources analyst Seamus Levine-Wilkinson. "We already knew that [the nucleotide inhibitor] sofosbuvir [GS-7977] was safe and well tolerated very effective, although something to point out is that the Phase III data are not as strong as the Phase II data."

Sofosbuvir was combined with the protease inhibitor simeprevir in the first cohort and the Phase IIa study, and the virus was eradicated in all 80 of the genotype 1 null prior-responder patients with liver fibrosis.

"Certainly, we were expecting maybe not 100 percent [success], and probably the final data one or two patients will relapse, or someone will discontinue, but it still looks like it's going to be pretty strong," Levine-Wilkinson told BioWorld Today.

In previous clinical work, simeprevir "has done really well in patients who have significant liver fibrosis, and that's key," he added. "That tells you this drug is clean and well tolerated in patients who are sick, and that's what the experts are looking for. These data are going to make them feel [even] better about simeprevir."

They already felt pretty good about the drug, also known as TMC435, for which Medivir AB, of Huddinge, Sweden, has a partnership with Janssen Pharmaceuticals Inc., part of Johnson & Johnson, of New Brunswick, N.J.

"Five different companies [have] had a chance to look at simeprevir really closely and decided that this drug was a good drug to mix their drug with," Levine-Wilkinson said. "That tells you that probably the safety data look really, really good. Obviously, not everything gets released before the [new drug application is filed], but whatever they're holding back has convinced these companies" of simeprevir's worth, he said.

Among them is New York-based Bristol-Myers Squibb Co. (BMS), which has tested it with the NS5A replication complex inhibitor daclatasvir with satisfying early stage results that could provide BMS with an important competitive edge, Levine-Wilkinson said.

Meanwhile, in the Phase IIa trial with simeprevir plus sofosbuvir, only 19 patients have reached end of treatment so far, with only 14 having reached sustained viral response at the fourth week after stopping therapy (SVR4), PiperJaffray analyst Ian Somaiya wrote in a research report. But the early results appear convincing, even though one patient discontinued therapy because of an unspecified adverse event.

"We look for further confirmation of the [combo's] clinical profile and an indication of the optimal duration of therapy" later this week, when updated interim data – including the SVR4 for about 50 patients – will be presented, Somaiya wrote.

Guessing which of the potentially lucrative, all-oral HCV regimens will take the lead is "tricky," Levine-Wilkinson said, and depends how fast, and how far, the partnered compounds progress. "We need to see who goes into Phase III with whom," he said.

Foster City, Calif.-based Gilead, he pointed out, is developing its own therapies for genotype 1 HCV patients. Last November, Gilead reported strong results from a Phase II study with GS-5585, an in-house drug similar to daclatasvir, at the American Association for the Study of Liver Diseases.

Whatever the shakeout, developments in the HCV space do not bode well for the likes of Incivek (telaprevir, Vertex Pharmaceuticals Inc.) and Victrelis (boceprevir, Merck & Co. Inc.), Levine-Wilkinson said, though these were "revolutionary drugs when they launched."

Data with newer compounds have "gotten so impressive so quickly," he said. "Lots of pretty sober-minded international experts have told me that the interferon-free data for a lot of regimens is almost too good to be true, but you're seeing it with so many different drugs in so many different combinations that it really does seem like the dam broke, and the science just got to the point where a lot of companies were able to introduce attractive regimens."

Medivir's stock (SS:MVIRB) closed Monday at SEK90 (US$14), up SEK3.25. Gilead's shares (NASDAQ:GILD) ended the day at $43.87, up 42 cents.