FDA Approves Atogepant for Prevention of Episodic Migraines

Atogepant is a small-molecule antagonist of the calcitonin gene-related peptide (CGRP) receptor. Monoclonal antibodies targeting the CGRP receptor or ligand are approved by the FDA for migraine prevention, but these therapies must be injected. Until the September 2021 announcement, the FDA had approved oral small-molecule CGRP receptor antagonists for acute treatment of migraine attacks but not for prevention of migraine attacks.

“This approval reflects a broader shift in the treatment and management paradigm for the migraine community. QULIPTA provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” said Peter J. Goadsby, MD, PhD, DSc, University of California, Los Angeles, and King’s College, London, in an AbbVie news release.

The approval was based on the results of the ADVANCE trial, a phase 3, double-blind, randomized clinical trial and an earlier phase 2b/3 trial. In the ADVANCE trial, investigators found that oral atogepant decreased the number of days per month with migraine or headache in patients with episodic migraines.

Participants in the ADVANCE study included adults who averaged 4 to 14 migraine days per month in the 3 months before enrollment and during a 28-day baseline period. They also had a history of ≥1 years of migraine with or without aura. Participants were allowed to take acute therapies for migraine attacks but not preventive therapies.

A total of 910 patients were randomly assigned to receive 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo for 12 weeks. The mean age of participants was 41.6 years and 88.8% were women. The average number of migraine days at baseline was 7.5 to 7.9 for each group.

The mean number of migraine days per month for the 12 weeks of treatment decreased in all groups, but the decrease was greater in the atogepant groups. The mean difference from placebo was –1.2 days per month for the 10-mg dose, –1.4 days per month for the 30-mg dose, and –1.7 days per month for the 60-mg dose (P <.001 for each dose vs placebo).

The investigators found similar results for secondary end points, change in number of headache days per month, and number of days using medication for a migraine attack (for both outcomes, P <.001 for each dose vs placebo). More than half of participants taking any dose of rimegepant had a ≥50% reduction in the 3-month average number of migraine days per month (P <.001 for each dose vs placebo).

The most common adverse event associated with atogepant was constipation. Among the patients receiving atogepant, 6.9% to 7.7% reported constipation compared with 0.5% of those who received placebo. Atogepant was also associated with nausea and fatigue.

In the company’s announcement, AbbVie wrote that all doses would be marketed. Atogepant has not been tested in pregnant women or children.

Sources

AbbVie. FDA approves QULIPTA™ (atogepant), the first and only oral CGRP receptor antagonist specifically developed for the preventive treatment of migraine. News release. Published September 28, 2021. https://news.abbvie.com/news/press-releases/fda-approves-qulipta-atogepant-first-and-only-oral-cgrp-receptor-antagonist-specifically-developed-for-preventive-treatment-migraine.htm. Accessed August 16,2022.

Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the preventive treatment of migraine. N Engl J Med. 2021;385(8):695-706.