If approved, INP104 would be the first and only delivery system to explore the vascular-rich upper nasal space as a therapeutically viable treatment pathway.
Impel NeuroPharma announced that the FDA has accepted the company’s 505(b)(2) new drug application (NDA) for INP104 for the acute treatment of migraine headaches with or without aura in adults.
The FDA has tabbed September 6, 2021, as the scheduled prescription user drug fee act (PDUFA) target action date for INP104 after Impel originally submitted the NDA back in November 2020. If approved, it will become the first and only therapy to utilize the Precision Olfactory Delivery Technology (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,” Adrian Adams, chairman and chief executive officer, Impel NeuroPharma, said in a statement.
INP104, expected to be marketed as Trudhesa if approved, aims to optimize dihydroergotamine mesylate (DHE) for fast and lasting whole migraine relief, regardless of when in the migraine attack it is administered, without an injection. The drug is also designed to deliver a lower dose of DHE compared to other nasally administered, FDA-approved investigational products, and enables patients to benefit from the efficacy of the DHE without the adverse effects that are associated with delivery to the lower nasal space.
Impel’s pivotal phase 3 STOP 301 study (NCT03557333) was the basis for the NDA submission. In addition to the study meeting its primary objectives, there was no new safety signals or concerning trends in nasal safety findings following delivery of DHE to the upper nasal space during the 52-week study period.
The majority of the treatment-emergent adverse events (TEAEs) were mild and transient in nature within the 24-week Full Safety Set (FSS; n = 354). Nasal congestion (16.7%), nausea (7.9%), nasal discomfort (5.4%) and abnormal taste (5.1%) were among the most frequently reported TEAEs (≥5%) during the entire 24-week period.
There were no cardiac TEAEs reported, and no significant changes in mean heart rate observed over the 24-week period. Over the 52-week full study period, no serious adverse events (SAEs) were observed.
Overall, 74% and 90% completed the 24- and 52-week phases of the study, respectively. Pain relief from use of INP104 was observed in 66.3% of the patients in the exploratory patient-reported efficacy data in the FSS (n = 354). Furthermore, 38% of the group reported pain freedom and 52% had freedom from their most bothersome symptom (MBS) at 2 hours following their first dose of INP104.
The use of a rescue medication was not needed in 85% of patients who reported migraine attacks. Additionally, 16.3% of patients claimed initial onset of pain relief came as early as 15 minutes and continued to improve over time.
Impel noted that the STOP 301 trial is 1 of the largest longitudinal studies of DHE to date and was comprised of both the FSS and a Primary Safety Set. The Primary Safety Set was comprised of 185 patients who took an average of 2 or more treatments of INP104 per 28-day period during the 24-week treatment period.
Adams added, “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."