Hepatitis; PSI-938 and PSI-7977 Breaking Down The Media Frenzy

Last week we had a sneak peek at a small study being presented at this months EASL.

According to the recent media frenzy Pharmassets two oral drugs in development "PSI-938 and PSI-7977" showed in early-stage data that 15 out of 16 patients achieved an early/promising antiviral response after 14 days on treatment.

The HCV community, although excited about a regimen of "interferon free" therapy, keep it all in perspective and wait until Pharmasset conducts their phase II study of " interferon-free combinations" with an SVR endpoint, expected in mid-2011. For this community the bottom line is SVR.

You can look at "all" the abstracts that will be presented at the EASL by clicking here

The controversy

The EASL has an embargo in place until the data is presented at the meeting. However, a few investment websites released the data early, breaking the media embargo.

The Study Can Be Found At The EASL Website

"ONCE DAILY DUAL-NUCLEOTIDE COMBINATION OF PSI-938 AND PSI-7977"

You can view the abstract here.

What Study are we talking about, whats the big deal ?

The study included treatment-naïve, non-cirrhotic patients with HCV Genotype 1. The two drugs "PSI-938 AND PSI-7977" were tested in four different cohorts (see below) without using "interferon" over fourteen days. The study was deemed ; NUCLEAR Study .
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From the Nov "2010" Press Release;

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 - Part 1, Part 2

Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, less then 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 (no interferon) and combination nucleotide dosing.

The Four Cohorts;

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.

From the EASL ; Preliminary results , the public is welcome to view the abstract

The company is expected 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.
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