Exploratory efficacy of INP104 in patients using concomitant preventive migraine medications

Presented at the AHS Annual Scientific Meeting, June 9–12, 2022

Authors: Grant, J.; Vann, R.; Fitzpatrick, C.; Lieu, T.; Shrewsbury, S.B.; Aurora, S.K.

One sentence summary: INP104 was associated with improvements in self-reported exploratory efficacy in patients who did or did not use concomitant migraine preventive medications over 24 weeks of treatment.

Background: To investigate the exploratory efficacy of INP104 [dihydroergotamine mesylate (DHE) delivered nasally by Precision Olfactory Delivery (POD®) technology] for the acute treatment of migraine, in patients who did or did not use concomitant migraine preventive medications over 24 weeks of treatment.

Methods: STOP 301 was a Phase 3, open-label, 24-week safety and exploratory efficacy study with a 28-week extension period for a subset of patients. Patients treated migraine attacks with their “best usual care” during a 28-day screening period, followed by a 24-week treatment period in which patients self-administered INP104 (1.45 mg) nasally with self-recognized migraine attacks. eDiaries were completed daily to capture headache and migraine details. Concomitant (preventive) migraine medications were permitted during the study if stable (>30 days before screening) unless they were contraindicated for concomitant use with DHE. For this post hoc analysis, exploratory efficacy end points of self-reported

pain and most bothersome symptom (MBS) freedom at 2 hours post-INP104 were evaluated based on concomitant preventive migraine medications used during the study –none, topiramate, erenumab, or “other” (eg, propranolol, amitriptyline, onabotulinum toxin A, etc). Patients who used >1 preventive medication were included under each applicable group; therefore, patients could be listed more than once.

Results: A total of 354 patients self-administered ≥1 dose of INP104 over 24 weeks and comprised the full safety set. For this post hoc analysis, 254, 31, 7, and 29 patients used none, topiramate, erenumab, or other migraine preventive medications concomitantly at Month 0 (i.e. baseline), respectively. For patients who used none, topiramate, erenumab, or other preventive medications concomitantly, the mean number of INP104-treated migraine attacks were 2.2 (n = 226), 2.0 (n = 20), 2.8 (n = 4), and 2.4 (n = 21) at Month 6 compared with 3.1 (n = 292), 3.0 (n = 32), 3.6 (n = 7), and 3.4 (n = 31) at Month 1, respectively. For patients who did not use concomitant preventive medications, self-reported pain and MBS freedom at 2 hours post-INP104 were 30.1% and 47.4% at baseline (n = 254) compared with 36.1% and 53.6% at Month 6 (n = 172), respectively. For patients who used topiramate concomitantly, self-reported pain and MBS freedom at 2 hours post-INP104 were 32.6% and 50.7% at baseline (n = 31) compared with 31.1% and 51.7% at Month 6 (n = 15), respectively. For patients who used erenumab concomitantly, self- reported pain and MBS freedom at 2 hours post-INP104 were 22.3% and 47.4% at baseline (n = 7) compared with 33.3% and 41.7% at Month 6 (n = 4), respectively. For patients who used other preventive medications concomitantly, self-reported pain and MBS freedom at 2 hours post-INP104 were 35.3% and 49.4% at baseline (n = 29) compared with 25.3% and 38.3% at Month 6 (n = 17), respectively.

Conclusion: The exploratory efficacy of INP104 over 24 weeks of treatment demonstrated numerical improvements in self-reported pain and MBS freedom at 2 hours post-INP104 with most of the concomitant migraine preventive groups analyzed. Results suggest that INP104 may be an effective acute therapy for migraine in patients who are concurrently using preventive therapies.