REYVOW CV

The approval of Reyvow was based on data from two phase 3 trials, SAMURAI (ClinicalTrials.gov Identifier: NCT02439320) and SPARTAN (ClinicalTrials.gov Identifier: NCT02605174). Patients enrolled in these studies had a history of migraine with and without aura, were predominantly female (84%) and White (78%); the mean age was 42 years. Patients were allowed to take rescue medication 2 hours after taking study drug; opioids, barbiturates, triptans, and ergots were not allowed within 24 hours of study drug administration.

The primary endpoint of both studies was the effect on pain freedom (defined as a reduction of moderate to severe headache pain to no pain) at 2 hours and most bothersome symptom (MBS) freedom (defined as the absence of the self-identified MBS [photophobia, phonophobia, or nausea]) at 2 hours compared with placebo.

In the SAMURAI study, patients were randomly assigned to receive Reyvow 100mg (n=744) or 200mg (n=745) or placebo (n=742). The percentage of responders in the Reyvow 100mg, Reyvow 200mg, and placebo groups were:

• Pain free at 2 hours: 28.3% (difference from placebo, 13; P <.001), 31.8%, (difference from placebo, 16.5; P <.001) and 15.3%.
• MBS free at 2 hours: 41.2% (difference from placebo, 11.6, P <.001), 40.7% (difference from placebo, 11.1; P <.001), and 29.6%.
• Pain relief (defined as a reduction in migraine pain from moderate to severe to mild or none) at 2 hours: 54.0%, 55.3%, and 40.0%.

In the SPARTAN trial, patients were randomly assigned to receive Reyvow 50mg (n=750), Reyvow 100mg (n=754), Reyvow 200mg (n=750) or placebo (n=751). The percentage of responders in the Reyvow 50mg, 100mg, 200mg, and placebo groups were:

• Pain free at 2 hours: 28.3% (difference from placebo, 7.3; P =.006), 31.4%, (difference from placebo, 10.4; P <.001), 38.8% (difference from placebo, 17.8; P <.001) and 21.0%.
• MBS free at 2 hours: 40.8% (difference from placebo, 7.6, P =.014), 44.0% (difference from placebo, 10.8; P <.001), 48.7% (difference from placebo, 15.5; P <.001), and 33.2%.
• Pain relief at 2 hours: 55.9%, 61.4%, 61.0%, and 45.1%.

Effects on Driving

A randomized, double-blind, placebo- and active-controlled, 5-period crossover study was conducted in 90 healthy volunteers to determine driving performance (using a computer-based simulation) at 90 minutes after administration of Reyvow 50mg, 100mg, 200mg, alprazolam 1mg, and placebo. The primary endpoint was the difference from placebo in the Standard Deviation of Lateral Position (SDLP), a measure of driving performance. Results showed a dose-dependent impairment in driving performance at all doses of Reyvow.

In a separate randomized, double-blind, placebo- and active-controlled, 4-period crossover study, driving performance (using a computer-based simulation) was assessed in 67 healthy volunteers at 8, 12, and 24 hours after administration of Reyvow 100mg or 200mg. Diphenhydramine 50mg was used as a positive control. Results showed the mean SDLP did not reach the threshold for driving impairment at 8 hours or later after Reyvow administration.