Atogepant Meets Primary End Point for Chronic Migraine in Phase 3 PROGRESS Trial

Michael Severino, MD

Today, AbbVie announced that its oral calcitonin gene-related peptide (CGRP) receptor antagonist, atogepant (Qulipta), met its primary end point in the phase 3 PROGRESS trial (NCT03855137), demonstrating a statistically significant reduction in mean monthly migraine days (MMDs) compared with placebo in patients with chronic migraine (CM).¹

Across the 12-week treatment period, the 60-mg once-daily (QD) and 30-mg twice-daily (BID) doses met this end point, while also showing statistically significant improvements in all other secondary end points after adjusting for multiple comparisons. Based on the results from PROGRESS, AbbVie intends to submit a supplemental new drug (sNDA) to the FDA for the expanded use of atogepant to include the preventive treatment of CM.

Atogepant was approved in Sept 2021 as the first and only oral CGRP receptor antagonist for the preventive treatment of episodic migraine. PROGRESS, a double-blind, placebo-controlled, parallel-group study, included 778 patients with chronic migraine experiencing at least 15 or more headache days per month for more than 3 months. Each patient was randomized to receive 60-mg QD of atogepant, 30-mg BID of atogepant, or placebo, for a 12-week treatment period.

The modified intent-to-treat (mITT) population included 755 patients with evaluable headache eDiary data collected during the double-blinded treatment period. Across the 12 weeks of treatment, those in the 60 mg QD and 30 mg BID arms experienced decreases of 6.88 and 7.46 MMDs, respectively, compared with patients in the placebo arm, who had a decrease of 5.05 MMDs (60 mg QD vs placebo, P = .0009; 30 mg BID vs placebo, P <.0001; adjusted for multiple comparisons).

READ MORE: Day 1 Impact of Migraine Medications Highly Valued Among Patients

"AbbVie has nearly 12 years of experience in treating chronic migraine, a debilitating disease. We know that no two migraine patients are alike, so it is important for health care providers to have a variety of treatment options,” Michael Severino, MD, vice chairman and president, AbbVie, said in a statement.¹ "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 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."

The European Union-focused off-treatment hypothetical estimand (OTHE) population included 760 patients with evaluable headache eDiary data collected during the double-blind treatment period and the follow-up period. Results for this population were similar to that of the mITT, with patients in the 60-mg QD and 30-mg BID atogepant treatment arms experiencing decreases of 6.75 and 7.33 MMDs, respectively, compared with the placebo arm, which demonstrated a decrease of 5.09 MMDs (60-mg QD vs placebo, P = .0024; 30-mg BID vs placebo, P = .0001, adjusted for multiple comparisons).

Atogepant continued to show a safe and tolerable profile that was consistent to what had been previously observed. Constipation (60-mg QD: 10.0%; 30-mg BID: 10.9%; placebo: 3.1%) and nausea (60-mg QD: 9.6%; 30-mg BID: 7.8%; placebo: 3.5%) were among the most commonly reported (>5%) adverse events (AEs) in the trial. Most of these were mild or moderate in severity, and most cases did not lead to discontinuation. Serious AEs occurred in 2.7% of patients in the atogepant 60-mg QD group, 1.6% of those in the 30-mg BIG group, and 1.2% of those on placebo.

In the mITT, achievement of 50% reduction in MMDs, a key secondary end point, was reported by 41.0% and 42.7% of patients, respectively in the 60-mg QD and 30-mg BID atogepant arms, compared with 26% of those on placebo (all groups vs placebo, P ≤.0009). Results were similar in the OTHE population, with 40.1% and 42.1% of patients, respectively, in atogepant treatment arms demonstrating this reduction, compared with 26.5% of those in the placebo group (all dose groups vs placebo, P ≤.0024).

These data build on the pivotal phase 3 ADVANCE study (NCT02848326) results, which evaluated atogepant for the preventive treatment of episodic migraine (EM) and was the basis for the FDA’s approval of the drug in Sept 2021. That study included 873 patients with EM who were randomized 1:1:1:1 to receive a once-daily dose of oral atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks.²

In ADVANCE, atogepant demonstrated an ability to improve several prespecified, multiplicity-controlled secondary end points across the 12-week period. Those in the atogepant 10-, 30-, and 60-mg dose groups experienced decreases in mean monthly headache days of 3.9 (baseline, 8.4), 4.0 (baseline, 8.8), and 4.2 (baseline, 9.0) days vs a 2.5-day (baseline, 8.4) decline in the placebo arm (P <.0001 for all doses). These translated to 56%, 59%, and 61% of patients in the 10-mg, 30-mg, 60-mg dose groups, respectively, compared with 29% of patients in the placebo arm.

In May 2021, prior to atogepant’s approval, Lawrence Severt, MD, PhD, director, AbbVie, sat down to discuss how atogepant would fit in among an expanding migraine toolbox. In the video below, he breaks down the mechanistic benefits of atogepant and the positive findings from ADVANCE.

REFERENCES
1. AbbVie announces positive phase 3 atogepant (Qulipta) data for preventive treatment of chronic migraine. News release. AbbVie. March 10, 2022. Accessed March 10, 2022. https://news.abbvie.com/news/press-releases/abbvie-announces-positive-phase-3-atogepant-qulipta-data-for-preventive-treatment-chronic-migraine.htm

2. Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the preventive treatment of migraine. NEJM. 2021; 385:695-706. doi:10.1056/NEJMoa2035908