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Non-oral INP104 as an acute treatment for migraine

Despite an increase in the number of treatments available for migraine, there is still an unmet need for therapies with high efficacy and safety, with current treatment options not being representative of patients’ preferences nor specific individual needs. 1

Migraine is identified as being the leading cause of disability worldwide. The negative consequences due to this debilitating condition include decreased vitality and fatigue, emotional instability, decreased mental health, decreased physical health, and psychiatric comorbidities.2 When treating migraine attacks with acute medication, consistency of response is important. Research looking into the effects that may contribute to inconsistent responses observed in patients, has found evidence to suggest that gastroparesis and variability in gastrointestinal absorption may be responsible. Therefore, research has turned to the development of drugs which are administered non-orally, to avoid this clinical obstacle.3,4

The STOP 301 study (NCT03557333) was a multicentre, open-label, 24-week study, with a subset extending treatment to 52-weeks, evaluating the safety and tolerability of INP104. INP104 is a novel drug-device combination product that delivers dihydroergotamine (DHE) to the upper nasal cavity, using a Precision Olfactory Delivery (POD®) device. This method of delivery theoretically has the ability to provide enhanced and consistent drug absorption, whilst being non-invasive. A Phase I study provided favorable results on its safety profile and a similar pharmacokinetics profile to IV DHE from 20 minutes to 48 hours with a lower Cmax. 5

Results from the Phase III STOP 301 study suggest that INP104 is linked with higher rates of symptom freedom and that a single dose of INP104 was found to have higher rates of sustained efficacy for those who had obtained relief with INP104 for their first treated migraine.6,7 The findings also showed that treatment with INP104 was associated with low rates of migraine recurrence.7 Additionally, a post-hoc analysis, found that INP104 treatment showed high levels of consistency across multiple migraine attacks over the course of 24 weeks, with 17.6%, 59.6%, and 63.3% of patients achieving 100%, 75% to <100% or better, and 67% to <75% or better consistency thresholds, respectively. 4

These findings provide a positive outlook for the acute treatment of migraine. The FDA accepted a filing for the approval of INP104 earlier this year and has set a Prescription Drug User Fee Act (PDUFA) action date for September 6, 2021. If approved, INP104 will be the first therapy to use the novel delivery system targeting the upper nasal space. 3

Written by Sam Deanus

Reviewed by Marta Palhas

References:

  1. Vargas BB. Acute treatment of migraine. CONTINUUM: Lifelong Learning in Neurology. Aug 2018; 24(4), pp.1032-1051.
  2. Charles A. The pathophysiology of migraine: implications for clinical management. The Lancet Neurology. Feb 2018; 17(2):174-182.
  3. Impel NeuroPharma announces US Food & Drug Administration acceptance of new drug application for INP104 for the acute treatment of migraine. PRNewswire. Available from: https://www.prnewswire.com/news-releases/impel-neuropharma-announces-us-food–drug-administration-acceptance-of-new-drug-application-for-inp104-for-the-acute-treatment-of-migraine-301211380.html (Last accessed 16/07/21)
  4. Lipton RB, Nye BL, Hirman J, Shrewsbury SB, Aurora SK. Treatment consistency across multiple migraine attacks: results from the phase 3 open-label STOP 301 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P183.
  5. Aurora S, Jeleva M, Hocevar-Trnka J, et al. A long-term, open label Safety and Tolerability Study Of Precision Olfactory Delivery of DHE in Acute Migraine Treatment (STOP 301): Exploratory Efficacy Results. Neurology. Apr 2021; 96 (15 Supplement) 2490.
  6. Smith TR, Aurora S, Hocevar-Trnka J, Shrewsberry S. Acute treatment of migraine with INP104: exploratory efficacy from the phase 3 STOP 301 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P180.
  7. Tepper SJ, Ailani J, Shrewsbury SB, Aurora SK. Recurrence rates for INP104 for the acute treatment of migraine: results from the phase 33 STOP 301 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P179.