Here is the link to Pharmasset's EASL abstract on a combination of two of its HCV drugs. I'm not an expert in the HCV field so please give us laypersons the lowdown on this proof of concept trial.
The R1626 development was terminated because of new and unexpected toxicity found during its Phase IIb trial in 2008. However the drug had shown a robust efficacy when given with SOC.
Of note is that the 14 day trial by Pharmasset excluded cirrhotics i.e. they chose the more responsive (easier to treat) patients in the GT 1 population. I wonder if they excluded African Americans or other statistically hard to treat subpopulations as well. And of course a Phase 1B 14 day study in such a small number of patients does not tell you the real story about SVR 24 or potential side efffects of drugs or viral breakthrough six months after completing a course of treatment. It took the past 5 years for Vertex to demonstrate those details for TVR and the direct anti-viral market will be dominated by Vertex as a result.
R1626. I couldn't find how long it took for breakthrough to occur. This was a single drug though versus VRUS's combo. Breakthrough did occur though which is why they added interferon and that seemed to cause the side effects that doomed the drug. It's not clear from vertex's releases how long their own combo lasted before breakthrough occurred. Or how much breakthrough there was.
If this can work without adding interferon/Riba it would be very bad for Vertex long term so it needs to be followed closely.
I suspect that the data was cramped and crammed in order to make an appearance for EASL. They probably were hasty and will come to regret it later. Marketeers more than scientists.
The claimed [no resistance] is clearly stated on their slide for their NUCLEAR study presented this morning at the Cowen conf.. As AF pointed out, it is ludicrous to even mention the word for a trial that ended at Day 14. It is more absurd for analysts to take the Phase 1 data so seriously.
We only have to remember that most nucleoside analogs failed so far. Roche's R1626, Idenix drugs, etc. A research paper describing the trial data for R1626 stated identical claims as the VRUS management is doing right now. Ask what happened to R1626.
"[... None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus....."
How does he know that? It seems to me that by the above, Adam seems to be implying that he has some post 14 day info. Unless there is another abstract that I don't know about, Pharmasset abstrct quoted below does not give any hint about post 14 day follow up results. Here is the quote from the abstract:
"Results: 30 patients were enrolled in cohorts 1-3 with baseline HCV RNA values of 7.0, 6.2 and 6.3 log10 IU/mL, respectively. Monotherapy (14 days) and 7+7 day combinations were generally safe and well tolerated with no SAEs and no discontinuations. Steady-state pharmacokinetics from monotherapy (day 7) and the combination (day 14) confirmed the absence of clinically-relevant PK interactions between PSI-7977 and PSI-938. Monotherapy PSI-938, monotherapy PSI-7977, or combination PSI-938+PSI-7977 provided profound and consistent reductions in HCV RNA with HCV RNA < LOD (15 IU/mL) as early as day 3 of the monotherapy phase."
Here is a qoute from Pharmasset's 10Q at 12/31/2010.
PSI-938, an HCV guanine nucleotide analog polymerase inhibitor that is enrolling patients in Part 2 of a Phase 1 study with PSI-7977 in patients with HCV genotype 1. We plan to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid (calendar year) 2011.
As promising as the abstract's results appear to be, VRUS is only at the Phase I stage and has a long road ahead before possible commercialization.
Here is the link for the 10Q:
These are promising data but from a very early stage of development. In subsequent studies they need to demonstrate a high percentage of subjects with viral titre below LOD (limit of detection) in larger populations, with varying degrees of disease, and maintain a decent safety profile in order to compete with telapravir and other competitors that are closer to approval than is Pharmasset. They also need to have a decent drug interaction profile with many potential co-medications, not just with the two components of the Pharmasset treatment.