Could an all-oral agent to treat HCV be on the way?

Two week interim data for Pharmasset's Interferon/Ribavirin-free nuc-nuc combo is a long way from an SVR, but so far the company has earned bragging rights by having 15/16 subjects in this early phase trial go undetectable after two weeks. This is seemingly a pretty potent combo in comparison to Vertex's data with it's nuc VX-222 + Telaprevir + Peg Interferon + Ribavirin. Depending on the arm, that data topped out at 38-57% undetectability after 14 days in comparison to 94% with PSI-938 and PSI-7977. Pharmasset’s new landmark was enough for investors to spin like tops and goose the stock to new heights. Keep in mind that investors don’t always act rationally and It’s difficult to predict outcomes as all we know regarding viral kinetics and positive/negative predictive values comes from regimens that contain peg-inf plus ribavirin as its therapeutic backbone. If PSI-938 and PSI-7977 can retain 94% undetectable at four weeks, I’ll be proportionally reassured regarding this combo’s future. It will be interesting how the company defines when it’s time to stop therapy given that there isn’t an immunomodulator aboard. At what time points will the company declare EOT and SVR? An all oral combo would be an amazing paradigm shift for this disease state and will set the bar extremely high for drug developers looking to get into the HCV therapeutic category, but there’s a long road ahead.

Pharmasset Hep C Data Wows Investors

Adam Feuerstein
03/08/11 - 11:46 AM EST
PRINCETON, N.J. (TheStreet) -- Pharmasset(VRUS) shares are soaring on the release of new but very preliminary data that hints at a breakthrough, all-oral cure for hepatitis C.

Treatment with two oral drugs developed by Pharmasset resulted in 15 of 16, or 94%, of patients reporting undetectable levels of the hepatitis C virus after 14 days, according to interim results from a study released Monday.

These early data on the two Pharmasset drugs -- PSI-938 and PSI-7977 are the best reported to date by any company seeking to develop a new, all-oral therapy for hepatitis C. This Pharmasset effort is drawing even more attention because it potentially eliminates the need for patients to be treated with long-acting interferon, one of two drugs currently used to treat hepatitis C but which is difficult for patients to tolerate and causes many side effects.

Pharmasset shares rose 24% on Monday and were up another 8% to $66.92 on Tuesday.

The PSI-938 and PSI-7977 combination data were released Monday in a research abstract released online by the European Association for the Study of the Liver (EASL), which holds its annual meeting March 30 through April 3.

EASL makes research abstracts for its annual meeting freely available to the public but prohibits journalists from writing about the data contained in the research abstracts until they are presented at the annual meeting. TheStreet refuses to adhere to EASL's media embargo since these hepatitis C data are freely available online now and are impacting the stock prices of publicly traded companies developing hepatitis C drugs.

While investors are displaying great enthusiasm for the Pharmasset all-oral drug combination, the data from the study are very early. One particular risk seen in other, similar studies that omit long-acting interferon is the development of mutated hepatitis C virus that can quickly become resistant to drug treatment.

None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus, according to the research abstract, but so-called viral rebound may emerge as patients are treated longer, or when treatment is stopped and these patients are followed long-term to determine if they are truly cured.
Pharmasset owns full rights to both PSI-938 and PSI-7977. The company is developing another hepatitis C drug, RG7128, in partnership with Roche.

"We believe the full data of a 14-day combination of PSI-7977 / PSI-938 to be presented at the upcoming EASL could show proof of principle for a nuc-nuc combination and position Pharmasset as one of the front runners in the race to develop an interferon-free regimen, which is considered a Holy Grail in hepatitis C treatment," said Leerink Swann analyst Howard Liang in a note to clients Tuesday.

The EASL meeting at the end of the month will also feature data from other companies seeking to develop various combination treatments for hepatitis C.

Vertex Pharmaceuticals(VRTX) is studying a "quad" regimen consisting of two experimental drugs, VX-222 and telaprevir, combined with the current standard of care, long-acting interferon and ribavirin. An EASL research abstract released Monday reported treatment with Vertex's "quad" therapy resulted in 38-57% of patients with undetectable virus after two weeks and 86-87% undetectable after four weeks.

One potential competitive disadvantage to the Vertex quad is that patients still need to be treated with long-acting interferon, which requires weekly injections. Vertex previously reported disappointing results from an all-oral Hep C drug regimen that eliminated interferon.

Telaprevir is currently under review by regulators in the U.S. and Europe. The U.S. Food and Drug Administration is expected to make an approval decision on or before May 23.

Gilead Sciences(GILD) and Bristol-Myers Squibb(BMY) will also be presenting new data from Hep C combination drug studies at the EASL meeting later this month.

--Written by Adam Feuerstein in Boston.