Dihydroergotamine delivered to the upper nasal cavity (DHE-POD) (INP104; Impel NeuroPharma, Seattle, WA) effectively and safely relieved migraine pain in the STOP-301 phase 3 clinical trial (NCT03557333) study relieved migraines safely and effectively, with no new safety signals or concerning trends in nasal safety findings. Although DHE has a high response rate and sustained efficacy, use has been limited by its accessibility only as an invasive injectable or in other forms with high dosing variability.
In the STOP-301 study, 66.3% of participants attained pain relief and 38% of participants attained pain freedom at 2 hours following their first dose of DHE-POD. In the primary safety set (PSS) (n=185), 33.1% of participants who took an average of 2 or more DHE-POD treatments per 28-day period over 24 weeks attained pain freedom at 2 hours. Initial onset of pain relief began as early as 15 minutes for 16.3% of participants, which continued to improve over time. Additionally, sustained pain freedom was observed in the majority of participants, with 98.4% and 95% of participants reporting no recurrence of their migraine or use of rescue medications during the 24- and 48-hour periods after using DHE-POD during weeks 21 to 24.
Over 5,650 migraine attacks were treated during this evaluation of self-administered intermittent use of DHE-POD for up to 52 weeks and collected in a diary to explore efficacy of DHE-POD as assessed by participant-reported change from baseline migraine measures.
In the study, DHE-POD delivered 1.45 mg, less than 72.5% of the currently approved dose (2 mg). Optimal dosing is critical so participants may stand to benefit from the established efficacy profile of DHE-POD, without the potentially triggering undesired side effects that can be experienced with delivering higher doses of drug to the lower nasal space. The most frequently reported adverse events (≥5%) during the entire 24-week period were nasal congestion (15%), nausea (6.8%), nasal discomfort (5.1%), and unpleasant taste (5.1%).
Further analysis of the STOP-301 study will be ongoing and will be submitted for future publication. A new drug application (NDA) for DHE-POD will be submitted to the Food & Drug Administration (FDA) in the second half of 2020.
Monideep Dutt, MD; Jamika Hallman-Cooper, MD; Ekta Bery, MD; Mohammed Shahnawaz, MD; and Grace Gombolay, MD
Danielle S. Shpiner, MD; Crystal Dixon, MD; Melissa R. Ortega, MD; and Henry Moore, MD