Findings for atogepant from the phase 3 PROGRESS study will form the basis of a submission by AbbVie to FDA for a label expansion in the US.
A pivotal phase 3 study evaluating atogepant in adult patients with chronic migraine met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days (MMD) compared to placebo for both doses evaluated across the12-week treatment period; significant improvement was observed in all specified secondary endpoints, as well.
The announcement made today by AbbVie states that this data from the phase 3 PROGRESS trial will be used to support the company’s submission to the US Food and Drug Administration (FDA) to expand use of atogepant to include preventive treatment of chronic migraine.
Atogepant, an oral, small-molecule calcitonin gene–related peptide (CGRP) receptor antagonist, was approved in September 2021 (Quilipta) for the preventive treatment of episodic migraine, the first oral CGRP receptor antagonist to be developed specifically for preventive migraine treatment.
PROGRESS was a global phase 3 randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the preventive treatment of chronic migraine. Individuals diagnosed as having chronic migraine experience headache occurring on ≥15 days per month for >3 months and on at least 8 days per month the headaches have features of migraine, according to the AbbVie statement.
For PROGRESS, a total of 778 patients with at least a 1-year history of chronic migraine were randomized into 1 of 3 treatment groups: 60 mg atogepant once daily, 30 mg atogepant twice daily, or placebo.
The primary endpoint measured the reduction from baseline in MMD compared to placebo, for both doses, during the treatment period of 12 weeks.
Based on regulatory agency feedback, according to AbbVie, the US modified intent-to-treat (mITT) population included 755 patients with evaluable headache eDiary data collected during the study’s double-blinded treatment period
Based on the mITT population, patients receiving atogepant 60 mg once daily experienced a decrease of 6.88 MMD compared to patients receiving placebo; those in the group that received 30 mg of the study drug twice daily experienced 7.46 fewer MMD vs patients in the placebo arm; those patients experienced a decrease of 5.05 MMD monthly migraine days (60 mg vs placebo, p=0.0009; 30 mg vs placebo, p<.001, after adjustment for multiple comparisons).
Both doses of atogepant were associated with statistically significant improvements in all secondary endpoints for efficacy. A key secondary endpoint measured the proportion of patients that over the 12-week treatment period reached at least a 50% reduction in mean MMD.
Again, based on the mITT population, PROGRESS investigators reported that 41.0% of patients in the daily 60 mg atogepant arm and 42.7% of those in the twice-daily 30 mg dose arm achieved at least a 50% reduction in MMD, compared to 26.0% of patients in the placebo arm (all dose groups vs placebo, p≤.0009, adjusted for multiple comparisons).
The overall safety profile of atogepant in PROGRESS was consistent with safety findings in previous studies of the CGRP antagonist in an episodic migraine population.
The most common adverse events reported with a frequency ≥5% in at least 1 atogepant treatment arm, and greater than placebo, were constipation and nausea. Most events were reported as mild or moderate in severity and did not lead to discontinuation. No hepatic safety signals were identified and the investigator deemed the small number of serious adverse events during the study unrelated to the study treatment.
"We know that no two migraine patients are alike, so it is important for health care providers to have a variety of treatment options," said Michael Severino, MD, vice chairman and president, AbbVie. "These data and pending regulatory submissions solidify our commitment to our leading migraine portfolio to help the more than one billion people worldwide living with the [sic] migraine. We look forward to taking the next steps to potentially expand the use of atogepant in the United States to include the preventive treatment of chronic migraine in adults, and to working with regulatory agencies globally on additional submissions."
Full results from the Phase 3 PROGRESS trial will be presented at future medical meetings, according to AbbVie, and more information about the trial can be found at www.clinicaltrials.gov (NCT03855137).