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Reverset Phase II Study Shows Reduced Viral Load

ATLANTA, Feb. 11 /PRNewswire/ -- Pharmasset, Inc. today announced results from a Phase 2 study of Reverset, which is being co-developed with Incyte Corporation for the treatment of HIV-infected patients. The data was presented at the 11th Conference on Retroviruses and Opportunistic Infections in San Francisco by clinical investigator Robert Murphy, M.D., Professor of Infectious Diseases at Northwestern University. The study demonstrated a marked reduction in viral load of more than 1.7 log(10) after 10 days of monotherapy treatment with no serious drug related adverse events.

"Reverset is a drug with the potential to be the best in its therapeutic class. It is one of the most potent and promising anti-HIV agents in clinical development," remarked inventor and Professor Raymond F. Schinazi.

Reverset, a nucleoside analog that targets the HIV-1 reverse transcriptase enzyme, is being developed under an approved US FDA Investigational New Drug (IND) application for the treatment of HIV-infected individuals. Preclinical in vitro studies have shown that Reverset inhibits replication of drug-resistant HIV strains commonly seen after treatment with zidovudine (ZDV) and lamivudine (3TC).

About the Study Design

A total of 30 HIV-infected, treatment-naive individuals with CD4(+) cell counts > 50 cells/mm(3) and plasma HIV-1 RNA levels > 5,000 copies/ml were enrolled in a 10-day monotherapy dose escalation study. Subjects were randomized to one of three dose levels of Reverset - 50 mg, 100 mg, or 200 mg, or placebo, once-a-day for 10 days. Study medication was administered in a double-blind fashion. Plasma samples were taken for HIV-1 RNA predose, on days 1, 2, 4, 8, 10 of treatment, and on days 11, 14, 21, 28 and 38 in the follow-up phase. Plasma samples for virus genotyping were taken at baseline, at the end of treatment, and at the follow-up visits. Pharmacokinetic samples were obtained over the first 24 hours of dosing and again on day 10.

Phase 2 Study Results

Preliminary results from this ongoing study showed plasma pharmacokinetic values were linear with dose on days 1 and 10 of dosing. Mean day 10 plasma C(max) levels were 2.3 uM, 5.4 uM and 9.8 uM for the 50 mg, 100 mg and 200 mg daily doses, respectively. The mean viral load declines at the end of the treatment phase for the three dose levels were 1.67 plus or minus 0.24 log(10) at 50 mg, 1.74 plus or minus 0.32 log(10) at 100 mg, and 1.77 plus or minus 0.23 log(10) at 200 mg, with maximum decreases ranging from 1.2 to 2.3 log(10). Viral RNA levels slowly returned to baseline during the follow-up period. CD4(+) cell counts increased during the treatment phase, but returned to pretreatment levels during the follow-up period. No serious drug-related adverse events were reported and all adverse events were mild or moderate and occurred at similar incidences in the active and placebo groups.

"The potent in vivo antiviral activity and safety in the current study coupled with the in vitro susceptibility of drug-resistant HIV to Reverset is very encouraging. We are optimistic that the next study in antiretroviral-experienced subjects will further confirm the drug's activity on a broader patient population," noted Dr. Michael Otto, Pharmasset's Chief Scientific Officer.

"Pharmasset has diligently managed the clinical development of Reverset through this Phase 2 study, which is further testament to the company's business and scientific goals of successfully advancing new therapeutics for life-threatening diseases from discovery to the clinic," stated Dr. Abel De La Rosa, Pharmasset's Senior Vice President of Business and Scientific Development. "Going forward, our strategic collaborative license agreement with Incyte will provide the added support and clinical expertise to continue the rapid development of Reverset toward regulatory approval and commercialization."

Source: Pharmasset, Inc.

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