New Formulation of Dihydroergotamine for Acute Migraine Treatment Submitted to FDA for Approval

In the phase 3 open-label STOP 301 study (NCT03557333), participants with migraine who treated attacks with dihydroergotamine mesylate (DHE) (inp104; Impel Neuropharma, Seattle, CA) had pain relief (66.3%), pain freedom (38%), and freedom from their most bothersome symptom (MBS; 52%) 2 hours after a first dose. Over 5,650 migraine attacks were treated over 24 or 52 weeks in this pivotal study that is supporting the New Drug Application submitted to the Food and Drug Administration (FDA)

In 85% of reported migraine attacks, participants did not require rescue medication. Initial onset of pain relief as early as 15 minutes was reported by 16.3% of participants, which continued to improve over time. The STOP 301 study is 1 of the largest longitudinal studies of DHE to date.

“The submission of INP104 represents our first NDA and marks a major milestone for Impel as we rapidly advance our pipeline of differentiated, potentially transformative therapies for people living with CNS disorders,” said Adrian Adams, chairman and chief executive officer of Impel NeuroPharma. “Based upon the previously reported positive results of the STOP 301 study, we believe that INP104 has the potential to provide an important new option for people who need a fast, effective, and consistently reliable acute treatment of migraine headaches.” 

The phase 3 STOP 301 study enrolled 360 participants who had a documented diagnosis of migraine with or without aura, with at least 2 attacks per month for the previous 6 months. The full safety set was comprised of the 354 participants who received at least 1 dose of DHE. The primary safety set included the 185 participants who took an average of 2 or more DHE treatments per 28-day period during the 24-week treatment period. Of those enrolled, 74% (n=262) of participants completed the 24-week treatment period. 

The most common treatment-emergent adverse events (TEAEs) were nasal congestion (15%), nausea (6.8%), nasal discomfort, and unpleasant taste (5.1% each) with all other TEAEs being reported by less than 3% of participants. No treatment related serious adverse events, cardiac TEAEs, or deaths were observed in the study.