Replies to post #116360 on Biotech Values

[DewDiligence]

Thanks—I updated the “Who’s Who in All-Oral HCV Programs” link in the iBox to point to your post.

p.s. ABT has several HCV drug candidates and may be planning something with an all-oral regimen while holding its cards close to the vest.

p.p.s. IDX320 is officially dead, so IDIX does not currently have an oral combination for testing.

[iwfal]

HCV - 1st trial with shot at 100% cure:

BMS-790052 (NS5A Inhibitor) and BMS-650032 (NS3 Protease Inhibitor)

and IFN-Lambda +/- Rib

Reminder that 790052 and 650032 are the two DAAs that, without SOC, have shown the best effect in nulls. But still had >50% breakthroughs. In comparison the other arm of the same trial (same 2 DAAs plus SOC) had 100% SVR12.

http://clinicaltrials.gov/ct2/show/NCT01309932?term=790052+650032&rank=1

I'd say that BMY is aiming to have the first 100% (or close enough) cure to make it to market. And possibly with lower side effects that the competitors that have lower cure rates.

[dewophile]

bristol has expanded their NS5A/PI combo study in nulls and it now has an all oral arm (the 2 novel DAAs+rib)

http://www.clinicaltrials.gov/ct2/show/NCT01012895?term=bristol+hepatitis+c&rank=1

[DewDiligence]

47% of untreated HCV patients who visit a doctor to discuss treatment are being “warehoused” until DAAs are launched. (Source: 1Q11 Roche CC)

[DewDiligence]

In other GILD news, an all-oral phase-2 trial testing GS5885 + GS9451+ GS9190 + ribavirin is planned to begin as soon as the FDA clears the protocol.

GS5885 is an NS5A inhibitor, GS9190 is a non-nuke, and GS9451 is a PI that’s the successor to GS9256 (which is evidently defunct).

[DewDiligence]

Addendum—GILD’s phase-2 mentioned in #msg-62299871 is the first HCV trial testing a combination of four oral drugs.

[DewDiligence]

VRUS/BMY Start All-Oral Phase-2a Trial of PSI-7977 + BMS-790052

[There are six arms in a 3x2 matrix: the 3-element axis of the matrix includes an arm of 24w combination treatment with ribavirin, an arm of 24w combination treatment without ribavirin, and an arm of 1-weak lead-in on PSI-7977 monotherapy followed by 23w of combination treatment without ribavirin; the 2-element axis of the matrix has arms for genotype -1 and for genotype-2/3. Patients in all six arms are treatment-naïve. (See the bulleted items below.)

The collaboration between VRUS and BMY to conduct this trial of a nuke + NS5A inhibitor was made in Jan 2011 (#msg-58596259). The trial description is at http://clinicaltrials.gov/ct2/show/NCT01359644 . The primary endpoint is SVR, which is expected to be reportable in Sep 2012.]

http://finance.yahoo.com/news/AllOral-Combination-Study-prnews-1258256197.html?x=0&.v=1

›Source: Pharmasset
Thursday May 26, 2011, 6:45 am EDT

PRINCETON, N.J., May 26, 2011 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq:VRUS) announced today the initiation of a Phase 2a trial investigating the combination of Pharmasset's PSI-7977, a nucleotide polymerase inhibitor, and BMS-790052, Bristol-Myers Squibb Company's (NYSE:BMY) NS5A replication complex inhibitor, for the treatment of chronic hepatitis C (HCV). This trial is the result of a clinical collaboration agreement between Pharmasset and Bristol-Myers Squibb announced in January 2011.

"We are happy to announce the initiation of this important combination trial," stated William Symonds, Pharmasset's Senior Vice President of Clinical Pharmacology and Translational Medicine. "Recent data from Bristol-Myers Squibb's combination study demonstrated that individuals with HCV can be cured without the traditional interferon and ribavirin, but only if two potent DAAs are used and drug resistance is avoided. We believe Pharmasset's nucleotide analogs have demonstrated potent antiviral activity and a high barrier to resistance and therefore have the potential to be the future backbone of interferon-free treatment."

About the Trial

This Phase 2a trial is planned to enroll approximately 84 patients with chronic HCV genotypes 1, 2 or 3 who have not been treated previously. The primary endpoint of the trial is sustained virologic response (SVR). The trial will be conducted in the U.S. Subjects will be randomized equally across each of the following arms:

• PSI-7977 400mg QD for 7 days, then add BMS-790052 60mg QD for further 23 weeks in genotype 1 subjects;

• PSI-7977 400mg QD for 7 days, then add BMS-790052 60mg QD for further 23 weeks in genotype 2 or 3 subjects;

• PSI-7977 400mg QD and BMS-790052 60mg QD for 24 weeks in genotype 1 subjects;

• PSI-7977 400mg QD and BMS-790052 60mg QD for 24 weeks in genotype 2 or 3 subjects;

• PSI-7977 400mg QD, BMS-790052 60mg QD and ribavirin for 24 weeks in genotype 1 subjects;

• PSI-7977 400mg QD, BMS-790052 60mg QD and ribavirin for 24 weeks in genotype 2 or 3 subjects.‹

[DewDiligence]

That list of all-oral HCV programs is badly out of date. The question to ask, however, is whether it ought to be updated. Based on the thinking in #msg-69330570, I’m inclined to say that the answer is no.

Comments?

[DewDiligence]

How come no one is talking about Boehringer-Ingelheim’s all-oral HCV program? Maybe no one is talking about it because there isn’t much to say. In this PR from EASL, B-I’s 3-drug combo of BI 201335 (a PI), BI 207127 (a non-nuke), and ribavirin generated an uninspiring SVR12 rate of 59-68% after 16-28 weeks of treatment in a phase-2b trial of treatment-naïve genotype-1 patients:

http://finance.yahoo.com/news/phase-2b-study-boehringer-ingelheims-090000497.html

Oddly, trial arm D, in which BI 207127 was dosed BID, produced a higher SVR12 rate than trial arm B, in which BI 207127 was dosed TID (68% vs 61%).

A separate trial arm testing the 3-drug combo for 40 weeks has not yet reported SVR12 data, but who cares?