Biotech Values

[DewDiligence]

VRUS Starts Phase-2b Trial of PSI-7977

[PSI-7977 is VRUS’ second-generation HCV pyrimidine nuke (RG7128 is the first-generation one) that is as yet non-partnered. The phase-2b trial carries forward the two highest doses—200mg qD and 400mg qD—that were tested in phase-2a (#msg-49886718). The main portion of the trial is for treatment-naïve genotype-1 patients, but there is an open-label arm for genotype-2/3. For the geno-1 patients who are not in the control arm, the duration of therapy is response-guided, which is the industry-standard design for phase-2b and phase-3 HCV trials.

This is one of the first HCV efficacy trials to stratify patients by the IL-28B gene variant (#msg-53635672).]

http://investor.pharmasset.com/releasedetail.cfm?ReleaseID=501896

›Tuesday August 24, 2010, 6:50 am EDT

• Phase 2b response-guided study in patients with genotype 1 HCV to receive PSI-7977 200mg QD and 400mg QD in combination with pegylated interferon and ribavirin

• Genotype 2 and 3 patients will be enrolled in an open label arm investigating 12 weeks of PSI-7977 400mg QD plus pegylated interferon and ribavirin

• Interim Phase 2b data expected in first half of 2011

PRINCETON, N.J., Aug 24, 2010 /PRNewswire via COMTEX News Network/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in a Phase 2b study of PSI-7977, a nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (HCV). The trial will evaluate PSI-7977 200mg QD and 400mg QD in combination with pegylated interferon alfa 2a and ribavirin, the current standard of care (SOC) in patients with HCV genotype 1 who have not been treated previously.

"We look for the Phase 2b to further support the efficacy, safety and resistance profile of PSI-7977 over 12 weeks, and to confirm a dose for continued development," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Given the potent antiviral activity observed in the Phase 2a study and in vitro evidence for pan-genotype activity, we have also decided to include an exploratory, open label arm of patients with HCV genotype 2 and 3 who will receive a 12 week treatment regimen of PSI-7977 in combination with pegylated interferon and ribavirin. If successful, this shorter treatment regimen would be a first step toward defining a new treatment option for these patients."

About the Phase 2b Trial

The Phase 2b trial is anticipated to enroll approximately 125 patients infected with HCV genotype 1 who have not been treated previously. The primary endpoint of the trial will be the assessment of safety and tolerability of PSI-7977, in combination with SOC over 12 weeks with response-guided therapy allowing discontinuation of SOC at week 24 [for patients with undetectable VL at weeks 4 and 12]. The trial will be conducted in the U.S. Patients will be randomized (2:2:1) into one of 3 arms:

• PSI-7977 200mg QD in combination with SOC for 12 weeks, followed by 12 or 36 weeks of SOC;

• PSI-7977 400mg QD in combination with SOC for 12 weeks, followed by 12 or 36 weeks of SOC;

• A control arm of matching placebo with SOC for 48 weeks.

Patients receiving PSI-7977 will discontinue treatment at week 24 if they achieve an extended RVR (eRVR), defined as HCV RNA below the limit of detection (<15 IU/ml) at week 4 and maintained until week 12. Patients who do not achieve an eRVR and all patients on placebo/SOC will continue on standard of care until week 48. Patients will be stratified by IL28B status to ensure balance across cohorts.

In addition, approximately 25 treatment-naive patients with HCV genotype 2 or 3 will be enrolled in a fourth, open label arm, receiving PSI-7977 400mg QD with SOC for 12 weeks, with no SOC follow-up. Patients will be followed for an additional 24 weeks after discontinuation of all therapy to assess SVR.

Pharmasset anticipates reporting interim data from this trial in the first half of 2011.‹