Results for two Phase III clinical trials (BHV3000- 301 and BHV3000-302) of rimegepant a proposed treatment for migraine.- Biohaven Pharma.

Biohaven Pharmaceutical Holding Company Ltd. announced positive top-line results from both of its two Phase III clinical trials (BHV3000- 301 and BHV3000-302) of rimegepant (formerly known as BHV-3000), an oral CGRP receptor antagonist for the acute treatment of migraine. In each trial, rimegepant met the co-primary efficacy endpoints of superiority to placebo, at two hours post-dose, on pain freedom and freedom from the most bothersome symptom (MBS). Even without additional rimegepant dosing, or use of rescue medications, these studies showed an early separation from placebo and a profile of continued improvement over the dosing interval.

Pain freedom at 2 hours for rimegepant treated subjects in Study 301 and 302 was 19.2% and 19.6%, respectively, versus 14.2% (p < 0.03) and 12.0% (p < 0.001) in the placebo treated groups. The magnitude of the treatment effect over placebo at 2 hours or later ranged from 5% to 19% in Study 301 and 7% to 22% in Study 302. This continued improvement in pain freedom was observed in subjects who took a single dose of rimegepant without use of rescue medications. Patients treated with rimegepant also achieved statistically significant benefits, as compared to placebo at 2 hours post-dose, in freedom from the MBS (selected from photophobia, phonophobia or nausea). Freedom from the MBS for rimegepant treated subjects in Study 301 and 302 were 36.6% and 37.6%, respectively, versus 27.7% (p < 0.002) and 25.2% (p < 0.0001) for placebo.

In addition to efficacy observed on the co-primary registrational endpoints, onset of pain relief (defined as transitioning from moderate-to-severe pain to either no-pain or mild-pain) was observed early after rimegepant treatment with numerical separation evident between 30-45 minutes post-dosing. By two hours in both studies, after a single dose, pain relief was achieved in over 55% of rimegepant treated subjects. Pain relief is a clinically important secondary endpoint, often associated with reduced disability due to migraine attacks. Subjects with difficult-to-treat migraines, as defined by the need for prophylactic treatments including Botox, achieved improvements similar to the overall population in pain freedom, MBS, and pain reliefat 2 hours. Rimegepant was found to be both safe and well-tolerated in the two Phase III studies with a safety profile similar to placebo.

In particular, pooled liver function test (LFT) results showed that rimegepant was no more likely than placebo to increase aminotransferase (ALT or AST) levels above the upper limit of normal (ULN ). No single adverse event (AE) occurred with an incidence higher than 2% and overall AE rates in the rimegepant group were similar to placebo. The most common AEs (pooled analysis across both studies) seen in patients treated with rimegepant were similar to placebo (nausea 1.4% and 1.1%, respectively; UTI 1% and 0.7%, respectively).

Comment:In both trials, the drug met its co-primary endpoint of superiority over placebo on measures of pain freedom and freedom from bothersome symptoms at two hours post-dose. Despite meeting the studies' primary endpoints, the data was weaker than expected and sent shares of Biohaven down nearly 30%.