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Pharmasset Initiates Dosing in a Combination Study
of PSI-7977 and PSI-938 for Chronic Hepatitis C
  - Phase 1 combination study of a pyrimidine (PSI-7977) and purine (PSI-938) nucleotide analog in patients with chronic hepatitis C
- Interim data expected in first quarter of 2011

from Jules: one of the hottest stories at AASLD was this, the 2 nucleotides Pharmasset is developing, 938 & 7977. Analysts were saying the company could be bought for 1.5 billion, and the question was & is - will a major pharma company buy this biotech company, who also developed the nucleoside R7128 but is being developed by Roche in their HCV program. Considering the potency & resistance benefits of 938 & 7977 these 2 drugs could put an HCV program over the top by adding these 2 drugs to the ones a big pharma company is already developing. Of course the downside is these big pharma companies already have their own set of drugs and perhaps they dont need them and what if safety issues develop, but this is a very interesting story to follow.
PRINCETON, N.J., Nov. 30, 2010 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in Part 2 of a Phase 1 study. This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.
"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."
About the Phase 1 Trial
In Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, <15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days. Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days. The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy and combination nucleotide dosing. Approximately forty patients are expected to be enrolled into four cohorts as follows:
* PSI-938 QD administered as monotherapy for 14 days, followed by;
* PSI-938 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days and
* PSI-7977 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days, followed by;
* PSI-938 plus PSI-7977 QD for 14 days
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011. We also expect to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in interferon-free combinations with an SVR endpoint.
About Pharmasset
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 that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Combination of two complementary nucleotide analogues, PSI-7977 and PSI-938, effectively clears wild type and NS5b: S282T HCV replicons - Comparison with combinations of other antiviral compounds - (04/20/10)
Pharmasset Announces Results of a 28-day Phase 2a Study with PSI-7977 for the Treatment of Chronic Hepatitis C Infection - (10/28/10)
--94% or 93% of patients achieved undetectable HCV RNA levels following 28 days of treatment with PSI-7977 200mg or 400mg QD, respectively, in combination with Pegasys(R) and Copegus(R)
Pharmasset Reports Positive Preliminary Antiviral Data with PSI-938 for the Treatment of Hepatitis C - (10/28/10)
-- PSI-938 achieves a median 3.94 to 4.64 log10 reduction in HCV RNA after 7 days of monotherapy
AASLD: High Rapid Virologic Response (RVR) with PSI-7977 Daily Dosing plus PEG-IFN/RBV in a 28-day Phase 2a Trial - (11/08/10)
AASLD: Clinical Synergy of an Anti-HCV Nucleotide Analog with SOC: Viral Kinetics of PSI-7977 with SOC - (11/08/10)
AASLD: Pharmacokinetics, Safety, and Tolerability of PSI-352938, a Novel Nucleotide Polymerase Inhibitor for HCV, Following Single Ascending Oral Doses in Healthy Subjects - (11/08/10)
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