Poster Number-3 - Early Prediction of Response to INP104 for the Acute Treatment of Migraine

Early Prediction of Response to INP104 for the Acute Treatment of Migraine

Purpose:

Understanding the early prediction of response to acute therapies for migraine may help patients and health care providers optimize the acute management of migraine. Predictive models have the potential to individualize choice of acute medication class for migraine attacks through a simple data-driven approach. However, future research needs to improve on predictive models and then prospectively explore if improvement in the selection of pharmacological treatment gained from such treatment-response predictors lets patients and clinicians confidently alter management plans. INP104 is an approved drug-device combination product that delivers dihydroergotamine mesylate to the upper nasal space using Precision Olfactory Delivery (POD®) technology. Previously reported data from the phase 3 STOP 301 study in migraine patients showed that INP104 was well tolerated and associated with improvements in several outcomes of exploratory efficacy for the first INP104-treated migraine attacks, as well as across multiple migraine attacks over 24 and 52 weeks of treatment. The objective of this post hoc analysis was to determine if early treatment response to INP104 could predict response over consecutive migraine attacks.

Methods:

STOP 301 was a phase 3, open-label, single-group assignment study that assessed the safety, tolerability, and exploratory efficacy of INP104. Inclusion criteria included adult migraine patients with or without aura not qualifying as chronic migraine; having ≥2 migraine attacks per month for the previous 6 months and during the 28-day screening period; and being in general good health with no history of cardiovascular risk factors or diseases. The study comprised a 28-day screening period in which patients used their best usual care, a 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 for all patients. The percentage of patients who were overall ≥75% responders during Weeks 1-24 based on self-reported pain level after treatment for their first, first 2, and first 3 INP104-treated migraine attacks during Weeks 1-4 was evaluated. A ≥75% responder was defined as a patient who self-reported having at least three-quarters of their migraine attacks with mild or no pain 2 hours after INP104 over a given period. Pain levels included none, mild, moderate, or severe, and pain severity subgroups were based on the worst pain reported for a migraine attack during Weeks 1-4.

Results:

A total of 360 patients were screened and enrolled into the 24-week treatment period, with 354 patients who self-administered ≥1 dose of INP104 over 24 weeks. This post hoc analysis included 188 patients who had ≥4 INP104-treated migraine attacks over 24 weeks. The ≥75% response rates for Weeks 1-24 were 72.9% (51/70), 87.2% (34/39), and 94.4% (17/18) for patients with pain of none at 2 hours post-INP104 for the first, first 2, and first 3 INP104-treated migraine attacks during Weeks 1-4, respectively. The ≥75% response rates for Weeks 1-24 were 69.2% (45/65), 75.4% (52/69), and 89.1% (41/46) for patients with pain of mild at 2 hours post-INP104 for the first, first 2, and first 3 INP104-treated migraine attacks during Weeks 1-4, respectively. The ≥75% response rates for Weeks 1-24 were 35.0% (14/40), 32.6% (14/43), and 33.3% (17/51) for patients with pain of moderate at 2 hours post-INP104 for the first, first 2, and first 3 INP104-treated migraine attacks during Weeks 1-4, respectively. The ≥75% response rates for Weeks 1-24 were 8.3% (1/12), 15.0% (3/20), and 27.8% (5/18) for patients with pain of severe at 2 hours post-INP104 for the first, first 2, and first 3 INP104-treated migraine attacks during Weeks 1-4, respectively.

Conclusion:

Patients who self-report mild or no pain at 2 hours for their first 3 INP104-treated migraine attacks are extremely likely ( >89%) to be a ≥75% responder over Weeks 1-24, and those with mild or no pain for their first 2 INP104-treated migraine attacks are likely ( >75%) to be a ≥75% responder over Weeks 1-24. Results suggest that if INP104 provides pain relief for the first 2-3 migraine attacks, it is likely a patient will continue to be an INP104 responder with long-term use. This predictability of response should be able to help clinicians determine a treatment armamentarium for appropriate patients. 

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