Treatment with INP104 was associated with high rates of symptoms freedom and may be a promising new acute treatment for patients with migraine.
Results from the phase 3 open-label STOP 301 study (NCT03557333) demonstrated that treatment with INP104 (Impel NeuroPharma) is associated with improvements in several migraine measures, with low recurrence rates, and is consistently effective throughout a 24-week stretch. The data was published across 3 abstracts which were presented at the 2021 Virtual American Headache Society (AHS) 63rd Annual Scientific Meeting, June 3-6.1-3
INP104, an investigational drug-device product that targets dihydroergotamine mesylate (DHE) to the upper nasal cavity using Precision Olfactory Delivery (POD) technology, had safety, tolerability, and exploratory efficacy assessed in STOP 301. The study comprised of a 4-week screening period, 24-week treatment period for all patients, a treatment extension to 52 weeks for a subset of the patients, and a 2-week post-treatment follow-up period.1
In the 24-week full safety set (FSS), the mean number of migraine attacks (MAs) self-reported as pain- and MBS-free 2-hours post-INP104 ranged from 35.1% to 38.7% and 49.2% to 57.9% compared to 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 to 23.5% and 40.8% at baseline, respectively, in the 52-week FSS.
In total, 15% of MAs required a rescue medication over the 24-week stretch. 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.
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.
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-INP104.2
All told, the same or improved level of benefit with INP104 was observed in patients during weeks 13-24 vs weeks 1-12, indicating within-person consistency. Of those responding in 75 to less than 100% of MAs during weeks 1-12, the majority achieved the same or better level of response during weeks 13-24 (88.5%). Additionally, 65.2% of those who responded to 100% of MAs during weeks 1-12 remained at this threshold during weeks 13-24.
Results from a patient acceptability questionnaire (PAQ) and the Migraine Disability Assessment (MIDAS) were also examined based on consistency thresholds. As consistency of response increased, patient acceptability improved, and MIDAS scores declined.
Patients with consistency thresholds that were 67% or greater generally strongly agreed that INP104 consistently relieved their MAs and that they could return to normal activities earlier with INP104 compared to their previous medications. Similar rates were observed across all 3 consistency threshold groups in terms of requesting an INP104 prescription from a physician once available.
The investigators concluded, "the consistency of INP104 may be attributed to several factors, including the more consistent systematic availability due to absorption of DHE by POD delivery to the upper nasal space; the familiar pharmacology of IV DHE, which has a long-standing reputation for being efficacious; and the non-oral route of delivery that bypasses the gut.”2
Separate post-hoc analyses of STOP 301 data were also performed on self-reported exploratory efficacy data collected over 24 weeks. Recurrence was defined as the percentage of patients who self-reported an onset of a new headache prior to 24 or 48 hours post-INP104 in patients who had self-reported pain freedom at 2 hours post-INP104.3
At 24 hours post-INP104, recurrence was self-reported in 7.1% (9 of 126) of patients and rose to 14.3% (18 of 126) of patients at 48 hours for the first treated migraine. Pain freedom was self-reported by 38% (126 of 332) of patients at 2 hours after treating their first migraine with INP104. Additionally, sustained pain freedom was self-reported by 35.2% (117 of 332) and 32.5% (108 of 332) of patients at 24 and 48 hours post-INP104, respectively, for the first treated migraine. Rescue medication use was self-reported by 18.2% (63 of 347) of patients for the first INP104-treated migraine.
In January, the FDA accepted the company’s 505(b)(2) new drug application for INP104 for the acute treatment of migraine headaches with or without aura in adults.4 The scheduled prescription user drug fee act (PDUFA) target action date for the agent is September 6, 2021, after Impel originally submitted the NDA in November 2020. If approved, it will become the first and only therapy to utilize the POD technology.
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