Acute Treatment of Migraine with INP104: Exploratory Efficacy from the Phase 3 Open-Label STOP 301 Study

Poster presented at the 2021 American Headache Society (AHS) Virtual Annual Scientific Meeting.

Authors: Tim R. Smith, MD, Sheena K. Aurora, MD, Jasna Hocevar-Trnka, MD, Stephen B. Shrewsbury, MB ChB


Intravenous dihydroergotamine mesylate (DHE), although long used effectively to treat migraine, is invasive, frequently associated with side effects, and not suitable for self-administration. INP104 is a novel drug-device combination product, in development, that delivers DHE to the upper nasal space using a Precision Olfactory Delivery (POD®) device, designed to overcome the shortcomings of currently marketed DHE products.


To report exploratory, self-reported efficacy data for INP104 from the open-label, Phase 3, STOP 301 study.


STOP 301 was a 24-week safety study with a 28-week extension sub-study. Here we report the exploratory endpoints from the population completing the 24-week period. After a 28-day screening period during which subjects documented baseline frequency and characteristics of migraine attacks treated with “best usual care,” INP104 (1.45 mg) was self-administered nasally to treat self-recognized attacks. The primary objective of this study was to assess safety and tolerability, with a focus on nasal mucosal integrity and olfactory function. Exploratory objectives included assessments of migraine measures including freedom from both pain and most bothersome symptoms (MBS) at various defined time points over multiple attacks.


During Weeks 1-12, 354 patients treated 2,559 migraine attacks with INP104, reporting 39% and 55% pain freedom and MBS freedom, respectively. During Weeks 13-24, patients treated 1,736 migraine attacks and 35% and 51% reported pain- and MBS-free, respectively.

More migraine attacks were pain- and MBS-free 2 hours post-INP104 at each 4-week interval, generally consistently over the full 24 weeks. These exploratory efficacy results for the 52-week period were consistent with the 24-week data. 37% of migraine attacks were reported pain free at 2 hours, with 35% and 32% sustained pain freedom at 24 and 48 hours, respectively, during Weeks 1-24. Patients treated 4,257 migraine attacks initially with INP104 during Weeks 1-24. 649 (15%) of these required rescue medication. Over 24 weeks, 25%, 57%, and 60% of patients were 100%, 75%, and 67% responders (i.e. the proportion of patients who self-reported mild or no pain at 2 hours post-INP104 over 24 weeks), respectively.


Results suggest that INP104 was associated with high rates of symptom freedom and may be a promising new acute treatment for migraine.


Smith TR, Aurora SK, Hocevar-Trnka J, Shrewsbury SB, Acute Treatment of Migraine with INP104: Exploratory Efficacy from the Phase 3 Open-Label STOP 301 Study, 2021 American Headache Society (AHS) Virtual Annual Scientific Meeting.