Biotech Values

[DewDiligence]

Demystifying ABBV/ENTA’s SAPHIRE-1/2 Trials

ABBV/ENTA’s SAPHIRE-1 and -2 are likely to be the first two phase-3 trials of the nine (!) phase-3 trials including ABT-450 to report data (see #msg-90408583 for a description of all nine trials). What some investors may not realize is that SAPHIRE-1 and -2 are essentially safety trials insofar as there is no bona fide control arm for an efficacy comparison.

In SAPHIRE-1 and -2, half of the patients are randomized to immediately receive ABBV’s 5-drug cocktail (ABT-450, ABT-267/r, ABT-333, and ribavirin) for 12 weeks; the other half of the patients are randomized to receive only placebos for 12 weeks followed by the identical 5-drug regimen as the first arm for 12 weeks (http://www.clinicaltrials.gov/ct2/show/NCT01716585 , http://www.clinicaltrials.gov/ct2/show/NCT01715415 ).

Because HCV progresses relatively slowly and a patient’s condition does not deteriorate materially without treatment during a period as short as 12 weeks, SAPHIRE-1 and -2 have essentially no difference between the two trial arms with respect to efficacy.

With respect to safety, however, the control (i.e. delayed-treatment) arm can serve as a comparator to the immediate-treatment arm to establish the safety profile of ABBV/ENTA’s regimen, relative to placebo, during the 12-week treatment period.

Note: The only difference between SAPHIRE-1 and SAPHIRE-2 is that the former is for treatment-naïve patients and the latter is for treatment-experienced patients. All patients in both trials are genotype-1.