Impel NeuroPharma Announces NDA Acceptance of INP104 for Acute Migraine

Impel NeuroPharma announced the U.S. Food and Drug Administration (FDA) has accepted for review the company's 5O5(b)(2) New Drug Application (NDA) for INP104 for the acute treatment of migraine headaches with or without aura in adults. INP104 is dihydroergotamine mesylate (DHE) delivered directly into the vascular-rich upper nasal space using Impel's proprietary Precision Olfactory Delivery (POD®) technology. If approved, INP104 will be marketed under the trade name, TRUDHESA™, in the U.S. and will become the first and only therapy to utilize the POD technology, a novel delivery system that specifically targets the vascular-rich upper nasal space.

"The FDA's acceptance of our submission package for TRUDHESA™ marks another important step in our journey to bring an important new treatment option to patients who, despite recent treatment advances, are still in need of a fast, effective, and consistently reliable relief from their migraine," said Adrian Adams, chairman and chief executive officer of Impel NeuroPharma. "Our proprietary POD® technology has the potential to unlock the therapeutic viability of a previously untapped treatment pathway – the vascular-rich upper nasal space. We are hopeful that patients with migraine who are still in search of an acute treatment that is both non-oral and on-demand will have access to such an option later this year and look forward to working closely with the FDA as it completes its review of our application."

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of September 6, 2021, which reflects a standard 10-month review period and is consistent with the review timeline for a 505(b)(2) NDA submission.

Impel is focused on the development and commercialization of transformative therapies for patients living with central nervous system (CNS) disorders with high unmet medical needs, and TRUDHESA™ is the Company's first therapeutic candidate to be submitted for U.S. regulatory review.

The NDA submission for TRUDHESA™ is supported by safety results from the pivotal Phase 3 STOP 301 study, in which more than 5,650 migraine attacks were treated over 24 or 52 weeks. The study met its primary objectives, with no new safety signals or concerning trends in nasal safety findings observed for TRUDHESA™ following delivery of DHE to the upper nasal space. For the 24-week Full Safety Set (FSS) (n=354), the majority of treatment-emergent adverse events (TEAEs) were mild and transient in nature. The most frequently reported TEAEs, (≥5%) during the entire 24-week period were nasal congestion (16.7%), nausea (7.9%), nasal discomfort (5.4%), and abnormal taste (5.1%). No cardiac TEAEs were observed, and no significant changes in mean heart rate were observed over 24 weeks of treatment. No drug-related serious adverse events (SAEs) were observed over the entire 52-week study. Exploratory patient-reported efficacy data in the FSS (n=354) observed that 66.3% of patients reported pain relief, 38% of patients reported pain freedom, and 52% had freedom from their most bothersome migraine symptom (MBS) at two hours following their first dose of TRUDHESA™. In 85% of reported migraine attacks, patients did not report use of rescue medication. Initial onset of pain relief as early as 15 minutes was reported by 16.3% of patients, which continued to improve over time. The STOP 301 study is one of the largest longitudinal studies of DHE to date.

The Phase 3 STOP 301 study enrolled 360 patients at 36 sites in the U.S. who had a documented diagnosis of migraine headaches with or without aura, with at least two attacks per month for the previous six months. 354 patients received at least one dose of TRUDHESA™ and comprised the Full Safety Set. 185 patients who took an average of two or more treatments of TRUDHESA™ per 28-day period during the 24-week treatment period comprised the Primary Safety Set. Of those enrolled, 74% (n=262) of patients completed the 24-week treatment period. Reasons for treatment discontinuation included withdrawal by subject (n=25 [7.1%]), adverse events (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%]). A subset of 73 patients continued into a 28-week treatment extension period to 52 weeks total, of which 90% completed.