The US Food and Drug Administration (FDA) is calling for a new approach in the way companies develop drugs intended to treat active migraines, a type of severe, long-lasting headache often characterized by a patient's sensitivity to light and sound.
In a new draft guidance document issued on 21 October 2014, the agency's Division of Neurology Products focuses on how companies developing acute (as opposed to preventative) treatments for migraine can develop their products more predictably.
The guidance, Migraine: Developing Drugs for Acute Treatment, is somewhat typical in recommending a randomized, double-blind, placebo-controlled, parallel group design for trials supporting the marketing application for a migraine product. Regulators also said the use of an active control product in addition to a placebo would be acceptable.
Trial participants should be graded based on a five-point criteria system developed by the International Headache Society (IHC), and younger than 50 years of age ("to decrease the change of enrolling patients with other diagnoses"). While FDA said it prefers patients suffering from only migraine headaches, patients suffering from both migraine and traditional headaches may enroll so long as their headaches are distinguishable from one another.
The guidance also contains recommendations regarding desirable trial endpoints demonstrating efficacy. FDA recommends two co-primary endpoints: Having no headache pain two hours after being dosed with the experimental drug, and a reduction in "the most bothersome" migraine-related symptoms two hours after dosing.
The "most bothersome symptoms" will be unique to the patient, but should include an assessment of nausea, photophobia (light sensitivity) and phonophobia (sound sensitivity), FDA explained. Patients should be asked to assess their symptoms according to a four-point Likert scale, FDA added.
Secondary endpoints of interest to FDA generally focus on the duration of the patient's complete response to the migraine after treatment.
FDA also recommends that companies enroll "women of child-bearing potential who are practicing effective contraception" early on in the development process since migraine headaches disproportionately affect women, and especially young women. Sponsors should also expect to be required to conduct pediatric studies in support of their products under the Pediatric Research Equity Act (PREA), though these trials generally occur after the approval of a product. FDA said it encourages sponsors to begin discussions about these studies early since plans must be submitted to FDA "no later than 60 days after an end-of-phase 2 meeting."
The guidance is not meant to guide the development of products to reduce the frequency of migraines, FDA noted.
Migraine: Developing Drugs for Acute Treatment (FR)