Intranasal INP104, dihydroergotamine mesylate (DHE) delivered by a novel investigational device, was associated with high rates of efficacy for first-treated migraine and low rates of migraine recurrence, research presented at the American Headache Society virtual meeting showed.
Migraine recurrence rates associated with INP104 were 7.1% and 14.3% at 24 hours and 48 hours, respectively, reported Stewart Tepper, MD, of Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, in a post hoc analysis of data from the STOP 301 study.
Previous STOP 301 findings showed that 38.0% of patients reported pain freedom, 52.1% reported freedom from their most bothersome symptom, and 66.3% reported pain relief at 2 hours for their first INP104-treated migraine.
“The INP104 device propels DHE to a capillary-rich area in the upper nose for optimal drug delivery by the use of an HFA propellant,” Tepper said.
“One of the most useful features of DHE is that it tends to give a complete acute migraine treatment, that is, a pain-free response without return of headache and without need for retreatment or rescue medication — a one-and-done outcome,” he told MedPage Today.
“Migraine recurrence was defined differently in different acute studies in the past, which is why the International Headache Society definition of sustained pain freedom is now the standard,” Tepper added. “However, no matter how recurrence is defined, the INP104 formulation of DHE resulted in high sustained results and low recurrence, as predicted for acute treatment of migraine with DHE.”
STOP 301 was a pivotal, phase III open-label study that evaluated the safety, tolerability, and exploratory efficacy of INP104. The trial enrolled 360 patients at 36 sites in the U.S. who had a documented diagnosis of migraine with or without aura and at least two attacks per month for the previous 6 months.
Participants were provided with up to three doses per week of INP104 (1.45 mg in a dose of two sprays) to administer nasally with migraine attacks. They completed daily electronic diaries to capture headache and migraine details, headache medication usage, and most bothersome symptom severity.
In the post hoc analyses, researchers used self-reported STOP 301 data collected over 24 weeks. Among people who reported pain freedom 2 hours after using INP104, recurrence was defined as the percentage with onset of a new headache within 24 or 48 hours; sustained pain freedom was defined as the percentage with no other headache 24 or 48 hours post-INP104.
Of 126 patients who reported pain freedom 2 hours after using INP104 for their first treated migraine, nine people reported recurrence at 24 hours and 18 people reported recurrence at 48 hours.
A total of 117 people (35.2%) reported sustained pain freedom at 24 hours and 108 people (32.5%) reported sustained pain freedom at 48 hours post-INP104.
Rescue medication use was reported by 18.2% of patients for their first INP104-treated migraine. Only non-ergot, non-triptan acute treatments were allowed as rescue medication for patients who still had headache pain, and only after 2 hours had elapsed since INP104 administration.
STOP 301’s limitations include its reliance on self-reported data. INP104 has an FDA Prescription Drug User Fee Act (PDUFA) target action date of Sept. 6, 2021, developer Impel NeuroPharma said. If approved, INP104 will be marketed under the trade name Trudhesa in the U.S.
The study was supported by Impel NeuroPharma.
Tepper disclosed grants for research (no personal compensation) from Allergan, Amgen, Eli Lilly and Company, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano. He has consulted and/or participated in advisory boards (honoraria) for Aeon, Align Strategies, Allergan/AbbVie, AlphaSights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceuticals, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, CRG, Currax, Decision Resources Group, DeepBench, Eli Lilly, Equinox, ExpertConnect, GLG, Guidepoint, Healthcare Consultancy Group, Health Science Communications, HMP Communications, Impel, Krog and Partners, Lundbeck, M3 Global Research, Magellan Rx Management, Medicxi, Navigant Consulting, Neurolief, Nordic BioTech Advisors ApS, Novartis, Pulmatrix, Reckner Healthcare, Relevale, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, System Analytic, Teva, Theranica, Thought Leader Select, Trinity Partners, Xoc, and Zosano. He receives a salary from Dartmouth-Hitchcock Medical Center, American Headache Society, and Thomas Jefferson University. He has received CME honoraria from the American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Headache Cooperative of New England, Henry Ford Hospital, Inova, Medical Learning Institute; Peerview, Medical Education Speakers Network, Miller Medical Communications, North American Center for CME, Physicians’ Education Resource, Rockpointe, ScientiaCME, and WebMD.