FDA issues draft guidance on developing migraine prevention drugs

The US Food and Drug Administration (FDA) on Thursday released a draft guidance to help sponsors develop drugs to prevent migraines that offers recommendations on trial population, trial design, dose selection, efficacy endpoints and statistical considerations.

The agency defines migraines as a “chronic neurovascular disorder characterized by recurrent attacks of often severe headache, typically presenting with nausea, vomiting, and sensitivity to light and/or sound.”

Current pharmacological approaches include treating acute migraine attacks as they arise or reducing the frequency of migraine attacks as a preventive treatment. This guidance addresses preventive treatments; previous guidance addressed drugs for treating acute migraines in 2018. (RELATED: Draft and Final FDA Guidances Detail Development of New Drugs for Neurological Disorders, Regulatory Focus 15 February 2018)

The agency said the guidance “is intended to serve as a focus for continued discussions among FDA’s Division of Neurology II, sponsors, the academic community, and the public.”

Sponsors should enroll subjects that have a diagnosis of either chronic migraine or episodic migraine. The International Classification of Headache Disorders (ICHD) defines chronic migraines as headaches occurring on 15 or more days per month for more than three months while patients with episodic migraines have intermittent, recurrent attacks with or without aura, with headaches occurring on 14 or fewer days per month.

Trials should have a randomized, double-blind and placebo-controlled parallel group design, and FDA says that sponsors should ensure that trial sites and outreach efforts “are broad enough to allow for a representative sample of the population for which the drug may be indicated.”

The clinical trials should run for at least three months, while follow-up visits should take place at least one month or five half-lives after the last dose, whichever is longer.

Patients should avoid taking any concomitant medications in early trials until drug-drug interactions are better understood. In later stage trials, accompanying medicines can be used “assuming no important pharmacokinetic/pharmacodynamic drug-drug interactions are anticipated.”

Sponsors should try to enroll those younger than 50 to reduce chances of enrolling subjects with headaches attributable to other disorders that resemble migraines. Patients should be able to distinguish migraines from other types of headaches they are experiencing.

For episodic migraine trials, the primary efficacy endpoint should assess changes from baseline in the number of migraines per month. For chronic migraine trials, sponsors also may use the change from baseline in the number of monthly migraines.

In clinical studies, primary endpoints are typically reported by patients using patient-reported outcome (PRO) instruments. FDA said that other PRO instruments can be used as secondary endpoints to assess treatments. Yet sponsors that intend to include a PRO instrument in their development programs “should engage early with the review division.” For more information on using PROs, FDA advised sponsors to consult its April 2023 guidance. (RELATED: FDA issues last guidance in patient-focused drug development series, Regulatory Focus 5 April 2023)

Comments should be submitted within 90 days and sent here.

Draft guidance, Notice

FDA issues draft guidance on developing migraine prevention drugs

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