Replies to post #132795 on Biotech Values

[oc631]

but the FDA decided post hoc to run the second year in a blinded manner to collect additional safety data

It's quite clear the study was extended to 96-weeks over safety concerns. GILD's PR highlights the fact elvitegravir was once again non-inferior to Isentress at 96-weeks but gives us scant detail on safety. The fact separate high/low doses were used to prevent safety issues from occurring when combined with certain P.I.'s is reason to be sceptical.

Trial participants received either once-daily elvitegravir (150 mg or 85 mg) or twice-daily raltegravir 400 mg. Patients’ background regimens were based on the results of resistance testing and include a fully-active ritonavir-boosted protease inhibitor, and a second agent that was permitted to be a nucleoside or nucleotide reverse transcriptase inhibitor, etravirine, maraviroc or enfuvirtide. Due to known pharmacokinetic interactions, patients randomized to elvitegravir whose background protease inhibitor was either atazanavir [Reyataz] or lopinavir received an 85 mg dose of elvitegravir.

Considering the design of the phase 3 study I suspect elvitegravir (outside the Quad) will be labeled for use in treatment experienced and/or patients that have viral resistance to other therapies. As you pointed out (in our discussion on HCV) doctors tend to mix/match HIV drugs to see what works. This being the case expect the FDA advisory committee to pay close attention to elvitegravir's safety and PK profile in combination with other drugs. This alone may hold up Quad approval.

[genisi]

By prior agreement with the FDA, the study reported here is the only phase-3 trial GILD needs to support FDA approval of Elviegravir. (Why only one phase-3 study? I’ll make the answer a quiz.)

Originally there was a second tween trial i.e. pivotal non-inferiority evaluating elvitegravir vs raltegravir in treatment experienced patients enrolling patients from EU, Canada and Australia. The FDA agreed to combine them into one global trial and cut the patients number "Due to declining numbers of patients with unsuppressed viremia". See here:

http://clinicaltrials.gov/ct2/show/NCT00707733