The NDA is supported by the phase 3 STOP 301 trial, which included more than 5650 migraine attacks in patients with or without aura.
According to a recent announcement, Impel NeuroPharma has submitted a new drug application (NDA) to the FDA for its investigational migraine treatment, INP104 (dihydroergotamine mesylate; DHE). The therapy is delivered by Impel’s precision olfactory delivery (POD) platform.1
The NDA is supported by the phase 3, open-label STOP-301 study (NCT03557333) that included 360 patients with acute migraine, with or without aura, at 36 sites. The study included more than 5650 migraine attacks treated over the course of either 24 or 52 weeks. Over the entire 52 weeks, there were no reported drug-related serious AEs. In the Full Safety Set (n = 354), 66.3% of patients achieved pain relief and 38% of patients achieved pain freedom at 2 hours following their first dose of INP104.1,2
The Primary Safety Set (PSS), which included 185 patients, showed that 33.1% of patients who took an average of 2 or more doses of INP104 per the 28-day period during the 24-week treatment phase achieved pain freedom at 2 hours. Initial onset of pain relief began as early as 15 minutes for 16.3% of patients and continued to improve over time.
"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, Impel NeuroPharma, in a statement. "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."
Overall, 74% and 90% of patients completed the 24- and 52-week phases of the study, respectively. Sustained pain freedom was observed in the majority of patients, with 98.4% and 95% of patients reporting no recurrence of their migraine or use of rescue medications during the 24- and 48-hour periods after using INP104 during Weeks 21–24.
In the FSS, researchers deemed the majority of treatment-related adverse events (AEs) for the 24-week set as mild and transient. The most frequently reported AEs (occurring at a rate ≥5%) were nasal congestion (15.0%), nausea (6.8%), nasal discomfort (5.1%), and unpleasant taste (5.1%). Withdrawal by subject (n = 25; 7.1%), AEs (n = 24; 6.8%), lack of efficacy (n = 21; 5.9%), lost to follow-up (n = 11; 3.1%), non-compliance/protocol violation (n = 5; 1.4%) and physician’s decision (n = 1; 0.3%) were all reported reasons for treatment discontinuation.
In June, Stephen B. Shrewsbury, MD, chief medical officer, Impel NeuroPharma, said in a statement that the company “believe[s] that these data add to the growing body of clinical evidence supporting the potential of INP104 to be a transformative new therapy for acute migraine. In addition to the STOP 301 study demonstrating INP104's potential to be both safe and well-tolerated when delivered to the upper nasal space, the data showed unsurpassed and sustained patient-reported pain freedom and pain relief rates compared to the best usual care in our exploratory efficacy analyses.”2
INP104 is the first and only product designed to deliver a lower dose of DHE compared to FDA-approved and investigational products in development to the vascular-rich upper nasal space. The agent aims to optimize DHE for fast and lasting migraine relief, regardless of when in the migraine attack it is administered, without an injection.