Replies to post #139782 on Biotech Values

[iwfal]

This was also a four drug combo I believe. Isn't the goal likely to get to three DAAs, at most, in future HCV therapy? How competitive will a four drug HCV combo be in the face of fairly effective three, or perhaps two, drug HCV combos assuming efficacy/safety is reasonably comparable?

Co-Pilot was a 3 drug combo and the Enanta PR said about it:

In the study known as "Co-Pilot," different doses of ABT-450/r, plus ABT-333 and ribavirin administered for 12 weeks showed sustained virological response at 12 weeks post treatment (SVR12) in 93 percent and 95 percent of treatment-naive genotype 1 (GT1) patients. In these patients, response was independent of HCV subtype, host IL28B genotype or dose of ABT-450/r. In addition, SVR12 was achieved in 47 percent of patients who were previous non-responders to past HCV treatment.

...

The objectives of this phase 2 study were to assess safety and tolerability 12-week interferon-free regimens in HCV GT1 patients who were either treatment naive or previous non-responders. The trial had three arms with three primary end points – rapid virological response (RVR) at week 4 and SVR at weeks 4 and 12.
•Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.
•95 percent (18 of 19) of treatment-naive patients infected with HCV GT1
(17 GT 1a, 2 GT 1b) achieved SVR12 with ABT 450/r 250/100 mg dosed once daily (QD) + ABT-333 400 mg dosed twice daily (BID) + ribavirin (Arm 1).
•93 percent (13 of 14) of treatment- naive patients infected with HCV GT1
(11 GT 1a, 3 GT1b) achieved SVR12 with ABT 450/r 150/100 mg QD + ABT-333 400 mg BID + ribavirin (Arm 2).
•47 percent (8 of 17) of patients with HCV GT1 (16 GT1a, 1 GT1b) who had previously not responded to other HCV treatments achieved SVR12 with ABT 450/r 150/100 mg QD + ABT-333 400 mg BID + ribavirin (Arm 3).
•One patient in Arm 1 discontinued due to asymptomatic isolated ALT/AST elevations at week 2. One patient in Arm 2 discontinued due to noncompliance in week 1. All remaining patients in Arms 1 and 2 completed treatment and achieved SVR12. In Arm 3, six patients experienced viral breakthrough while on treatment and three patients relapsed after treatment stopped.
•In the trial the most common adverse events were fatigue (42 percent), nausea (22 percent) and headache (20 percent).
Abbott is developing ABT-450 with low dose ritonavir (ABT-450/r) which enhances the pharmacokinetic properties of ABT-450, allowing for once daily dosing. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational.

http://www.pharmalive.com/News/Index.cfm?articleid=833531

I think a key point, missed in other PRs, is that the trial was heavily loaded with G1a patients so these PR'd SVRs are really the SVRs in G1a's. The only remaining questions are:

a) What happens without Rib (which is a SAE drug)?

b) What are the SAE of the two new DAAs? (e.g. what happened with the liver tox issue)?

[DewDiligence]

ABT/ACHN/Medivir— does anyone take the success of ABT-450, the PI, as part of this combo as bearish for the other 2nd gen HCV PI candidates such as those from Medivir and ACHN?

No—if anything, I would say it’s modestly bullish for the other second-generation PI’s.

[oc631]

Isn't the goal likely to get to three DAAs, at most, in future HCV therapy? How competitive will a four drug HCV combo be in the face of fairly effective three, or perhaps two, drug HCV combos assuming efficacy/safety is reasonably comparable?

Of course fewer drugs would be a net positive. Removing ribavirin from the mix would certainly make other oral offerings more tolerable with the potential for QD dosing. Investor focus should be centered on who will be first to market in GT1 oral. If GS-7977/Riba lacks potency in GT1 treatment-naive patients this could be a close race.

Data from the GS-7977/BMS-052 combo study will be released in a couple of weeks. Even if the data is good it's unclear if the companies are willing to work together. If we see impressive data my feeling is GILD will start testing GS-7977 with their in-house NS5A and BMY will test BMS-052 with BMS-189.

Separately, does anyone take the success of 450, the PI, as part of this combo as bearish for the other 2nd gen HCV PI candidates such as those from Medivir and ACHN?

ABT-450 needs ritonavir boosting so in that respect there's room for improvement.

[genisi]

Results from the CO-PILOT study also bode well for VRTX' oral combo (Incivek + VX-222 +Riba) although if memory serves SVR4 there were nowhere near those from CO-PILOT.