Replies to post #99964 on Biotech Values

[DewDiligence]

Curiously, VRUS’ phase-1b trial runs for seven days, which is four days longer than the typical 3-day limit imposed by the FDA for US monotherapy studies in HCV patients.

[genisi]

Pharmasset Reports Positive Preliminary Antiviral Data with PSI-938 for the Treatment of Hepatitis C

http://investor.pharmasset.com/releasedetail.cfm?ReleaseID=524015

PRINCETON, N.J., Oct 28, 2010 /PRNewswire via COMTEX News Network/ -- Pharmasset, Inc. (Nasdaq: VRUS) reported positive preliminary results today from its phase I monotherapy trial of PSI-352938 ("PSI-938") for the treatment of chronic hepatitis C (HCV). PSI-938 is a guanosine nucleotide analog polymerase inhibitor in development for the treatment of chronic HCV infection.

PSI-938 Phase 1 Multiple Ascending Dose Study Overview

In August 2010, Pharmasset initiated a phase 1 multiple ascending dose study with PSI-938 administered once daily (QD) or twice daily (BID) for 7 days. The trial was conducted at two US centers as a blinded, randomized, and placebo-controlled study in 40 patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability, and pharmacokinetics of PSI-938 administered over 7 days. The secondary objective was to assess antiviral activity by measuring the change in HCV RNA. Patients were randomized within each cohort to receive either PSI-938 (8 patients per cohort) or placebo (2 patients per cohort). Four dose cohorts of PSI-938 (100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID) have been completed.

PSI-938 Antiviral Activity Summary

Preliminary Antiviral Response Observed Following PSI-938
Administered as Monotherapy for 7 Days

    Dose           n    Median Change in       Range      Number of Subjects with 
                     HCV RNA at Day 8                          HCV RNA 
                       (log10 IU/mL)    (log10 IU/mL) <LOD           <LOQ 
     100 mg QD     8             -4.31 -2.66 to -5.12       1                 3 
     200 mg QD     8             -4.64 -3.49 to -5.35       5                 7 
     300 mg QD     8             -3.94 -3.43 to -5.29       4                 4 
     100 mg BID    8             -4.59 -3.94 to -5.08       2                 3 
     Placebo       8             -0.05 +0.17 to -0.29       0                 0 
     -------     ---             ----- --------------   

--- ---



LOD = limit of detection (<15 IU/mL)
LOQ = limit of quantification (<43 IU/mL)



PSI-938 demonstrated potent antiviral activity with a mean HCV RNA change from baseline of 4.31 log10 IU/mL, 4.64 log10 IU/mL, 3.94 log10 IU/mL and 4.59 log10 IU/mL in patients receiving 100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID for seven days, respectively. HCV RNA declined consistently throughout the 7-day dosing period, with no viral breakthrough. For the 16 subjects who received PSI-938 200 mg QD or 300 mg QD for 7 days, more than half (9 of 16) of the subjects on PSI-938 monotherapy achieved HCV RNA below the limit of detection (15 IU/mL) and 11 out of 16 patients achieved HCV RNA below the limit of quantification (43 IU/mL).

PSI-938 Pharmacokinetic and Safety Summary

Pharmacokinetics parameters were similar between healthy subjects in the single ascending dose study and HCV infected patients in the seven-day multiple ascending dose study. PSI-938 at all doses provided good systemic exposure and continue to support once-daily administration.

PSI-938 was generally safe and well tolerated across all doses studied to date with no serious adverse events and no discontinuations. There were no dose-related trends in adverse events through the dose escalations, no grade 4 treatment emergent laboratory changes, and no trends in clinical laboratory abnormalities.

PSI-938 SAD and preclinical data

The Phase 1a single ascending dose study conducted earlier this year assessed single doses of PSI-938 ranging from 100 mg to 1600 mg or matching placebo in healthy male and female volunteers. No dose-limiting toxicity was identified. Safety and pharmacokinetic data supported progression of PSI-938 to the 7-day monotherapy trial. Full data from the SAD trial will be presented at the upcoming AASLD Annual Liver Meeting in Boston, MA, October 29-November 3, 2010 (poster #1890).

Preclinically, both PSI-938 and Pharmasset's other guanosine analog, PSI-661, which is in late preclinical development, have demonstrated similar potency against wild-type HCV or HCV with the S282T mutation, which can be selected by RG7128 and PSI-7977 in vitro. Although the S282T has not been detected in treatment-naive individuals with HCV, nor selected in clinical trials with any of Pharmasset's nucleoside/tide analogs, the potential for interferon-sparing regimens may increase the focus on antivirals with complementary resistance profiles.

"We are very encouraged by the preliminary efficacy and safety data with PSI-938, our purine nucleotide analog for HCV," said Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "These data provide the first confirmatory evidence that a nucleoside/tide analog can exhibit substantial early antiviral activity in monotherapy as has been observed with compounds in other DAA classes. Unlike other classes of DAAs to date, our nucleotide analogs also provide a higher barrier to resistance and clinically-validated antiviral activity across a broad range of HCV genotypes, characteristics not yet demonstrated with other classes of DAA. We continue to believe that nucleoside/tide analogs will become the backbone of HCV therapy. In addition, similar to HIV, the combination of two complementary nucleoside/tide analogs could provide a differentiated therapy for HCV patients in the future."

PSI-938 and PSI-7977 Combination Study

In this quarter, Pharmasset plans to initiate a short-term study to assess the combination of PSI-938 and PSI-7977. The trial will be conducted in the US, as a blinded, randomized, placebo-controlled study in approximately 50 patients chronically infected with HCV genotype 1. The primary objective will be to assess the safety, tolerability, and pharmacokinetics of PSI-938 and PSI-7977 alone and in combination. Preliminary results are expected in the first half of 2011.