PRINCETON, N.J., Oct. 28 /PRNewswire-FirstCall/ -- 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
Median Change in
HCV RNA at Day 8
Number of Subjects with
100 mg QD
-2.66 to -5.12
200 mg QD
-3.49 to -5.35
300 mg QD
-3.43 to -5.29
100 mg BID
-3.94 to -5.08
+0.17 to -0.29
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.
Conference Call and Webcast
Members of Pharmasset's management team will host a conference call today, October 28, 2010, at 8:00 a.m. ET to discuss the preliminary results of the multiple ascending dose trial with PSI-938. Investors may listen to the webcast of the conference call live on the "Events & Presentations" section of Pharmasset's website, www.pharmasset.com. Alternatively, investors may listen to the call by dialing 877-771-7028 from locations in the U.S. and 973-200-3092 from outside the U.S. The webcast replay will be available for at least 72 hours following the call.
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog presently in a Phase 2b study, and PSI-938, an unpartnered guanosine nucleotide analog in Phase 1. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.
Pegasys® and Copegus® are registered trademarks of Roche.
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +1 (609) 613-4181
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2009 and our Quarterly Reports on Form 10-Q for the periods ended December 31, 2009, March 31, 2010 and June 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.