Impel’s agent is designed to deliver a lower dose of dihydroergotamine mesylate (DHE) compared with other nasally administered products.
The FDA has approved Impel NeuroPharma’s INP104 nasal spray for the acute treatment of migraine headaches with or without aura in adults. Marketed as Trudhesa, it is the first and only approved therapy that utilizes the Precision Olfactory Delivery (POD) technology, a novel delivery system that specifically targets the upper nasal space.1
INP104's intranasal administration optimizes dihydroergotamine mesylate (DHE) for fast migraine relief regardless of when in the migraine attack it is administered. The drug delivery system is also designed to deliver a lower dose of DHE compared with other nasally administered, FDA-approved products, in turn reducing the adverse effects that are typically associated with delivery of DHE to the lower nasal space.
The FDA’s decision was based on data from the phase 3 STOP 301 study (NCT03557333), in which INP104 met the primary end point and demonstrated no new safety signals or concerning trends in nasal safety findings during the 52-week study period. The data were included in Impel's new drug application (NDA), which was filed in November 2020 and accepted in January of this year.2
"We are delighted with the approval of Trudhesa and are proud to offer the millions of Americans with migraine a non-oral, acute treatment option that may provide rapid, sustained, and consistent relief, even when taken late into a migraine attack," said Adrian Adams, chairman and chief executive officer, Impel NeuroPharma, in a statement.1 "The approval of Trudhesa marks the culmination of more than a decade of research and advanced engineering to pair the proven efficacy of DHE with our innovative POD technology."
Overall, 74% and 90% of patients completed the 24- and 52-week phases of the study, respectively. Efficacy data in the Full Safety Set (FSS) showed that 66.3% of the patients experienced pain relief with treatment. 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.
In the 24-week FSS, the majority of treatment-emergent adverse events (TEAEs) were mild and transient in nature. The most frequently reported TEAEs (≥5%) during the period were nasal congestion (16.7%), nausea (7.9%), nasal discomfort (5.4%), and abnormal taste (5.1%). Notably, investigators did not observe any cardiac TEAEs, as well as no significant changes in mean heart rate. No serious adverse events were recorded over the 52-week period.
Open-label results from STOP 301 were presented at the 2021 American Headache Society 63rd Annual Scientific Meeting, June 3-6. Data presented showed that INP104 was associated with improvements in several migraine measures, low recurrence rates, and consistent efficacy over 24 weeks.3-5
The mean number of migraine attacks self-reported as pain- and MBS-free 2-hours post INP104 dosing ranged from 35.1% to 38.7% and 49.2% to 57.9% compared with 30.6% and 47.9% at baseline, respectively. At 52 weeks, the mean number of MAs self-reported as pain- and MBS-free 2-hours post-INP104 ranged from 31.4% to 39% and 39.8% to 55.7% compared with 23.5% and 40.8% at baseline, respectively. In total, 15% of MAs required a rescue medication over the 24-week period. Despite allowing a second INP104 dose within 24 hours, 90.9% of those opted to use non-INP104 medications in lieu of the second optional dose.
"Many of my patients need more from their migraine treatment, and Trudhesa offers a non-oral, fast-acting, reliable option that overcomes many current medication challenges,” Stephanie J. Nahas-Geiger, MD, MSEd, associate professor, and program director of the Headache Medicine Fellowship Program, Thomas Jefferson University, said in a statement.1 "Its upper nasal delivery circumvents the GI tract and common phenomena associated with migraine, such as nausea and gastroparesis, that can impact the effectiveness of oral treatments. And, importantly, it is a self-administered, single dose that can be taken anytime during a migraine attack, so patients don’t need to worry about missing the opportunity to benefit from using Trudhesa within a certain timeframe. I think patients will be very receptive to this treatment, because it pairs the long-proven benefits of DHE with a patient-friendly delivery system."
INP104 also demonstrated a significant consistency of response. Over 24 weeks, 25%, 57%, and 59.9% of patients were 100%, 75% or greater, and 67% or greater responders, respectively. After 24 weeks, 22.2%, 58.3%, and 65.3% of patients were 100%, 75% or greater, and 67% or greater responders, respectively.3
Treatment consistency was observed in a separate analysis that included 188 patients in the 24-week FSS who had 4 or more INP104-treated MAs in both weeks 1-12 and weeks 13-24. Within-person consistency in 2-hour headache response (2hHR) was defined as the proportion of treated MAs (100%, ≥75%, and ≥67%) having mild or no pain at 2 hours post-INP104.
Sheena Aurora, MD, vice president, Medical Affairs – Migraine, Impel, sat down with NeurologyLive at the conclusion of AHS 2021 to discuss the clinical takeaways from STOP 301 and the advantages INP104 may offer patients with migraine. Listen to her commentary below.
Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors. Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of TRUDHESA with strong CYP3A4 inhibitors is contraindicated.