Positive Data for Preventive Treatment of Chronic Migraine

Pivotal Phase 3 study evaluating atonement in adult patients with chronic migraine meets primary endpoint of statistically significant reduction from baseline in mean monthly migraine days compared to placebo across the 12-week treatment period.

AbbVie today announced that the Phase 3 PROGRESS trial evaluating atogepant (QULIPTA™ in the United States), an oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the preventive treatment of chronic migraine in adults, met its primary endpoint of statistically significant reduction from baseline in mean monthly migraine days compared to placebo, for both the 60 mg once daily (QD) and 30 mg twice daily (BID) doses, across the 12-week treatment period. The study also demonstrated that treatment with atogepant 60 mg QD and 30 mg BID resulted in statistically significant improvements in all secondary endpoints after adjustment for multiple comparisons.

This Phase 3, global, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of oral atogepant for the preventive treatment of chronic migraine, which is a debilitating neurological disease where patients experience headache occurring on 15 or more days per month for more than three months, which on at least eight days per month has features of migraine headache.2,3 A total of 778 patients with at least a one-year history of chronic migraine were randomized into one of three treatment groups to receive 60 mg QD of atogepant, 30 mg BID of atogepant, or placebo.

Efficacy was analyzed using two slightly different definitions of the patient population based on regulatory agency feedback in the United States and European Union. The United States-focused, modified intent-to-treat (mITT) population included 755 patients with evaluable headache eDiary data collected during the double-blinded treatment period. 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.

Across the 12 weeks, based on the mITT population, patients in the atogepant 60 mg QD and 30 mg BID treatment arms of the study, experienced a decrease of 6.88 and 7.46 monthly migraine days, respectively, compared to patients in the placebo arm, who experienced a decrease of 5.05 monthly migraine days (60 mg QD vs. placebo, p=0.0009; 30 mg BID vs. placebo, p<0.0001, adjusted for multiple comparisons).  Based on the OTHE population, across the 12 weeks, patients in the 60 mg QD and 30 mg BID of atogepant treatment arms of the study, experienced a decrease of 6.75 and 7.33 monthly migraine days, respectively, compared to patients in the placebo arm, who experienced a decrease of 5.09 monthly migraine days (60 mg QD vs. placebo, p=0.0024; 30 mg BID vs. placebo, p=0.0001, adjusted for multiple comparisons).

The study demonstrated that treatment with atogepant 60 mg QD and 30 mg BID resulted in statistically significant improvements in all secondary endpoints for both efficacy analysis populations.

A key secondary endpoint measured the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across the 12-week treatment period. Based on the mITT population, the trial demonstrated that 41.0%/42.7% of patients in the 60 mg QD and 30 mg BID atogepant arms, respectively, achieved at least a 50% reduction, compared to 26.0% of patients in the placebo arm (all dose groups vs. placebo, p≤0.0009, adjusted for multiple comparisons). Based on the OTHE population, the trial demonstrated that 40.1%/42.1% of patients in the 60 mg QD and 30 mg BID atogepant arms, respectively, achieved at least a 50% reduction, compared to 26.5% of patients in the placebo arm (all dose groups vs. placebo, p≤0.0024, adjusted for multiple comparisons). 1

The overall safety profile of the Phase 3 PROGRESS study was consistent with safety findings observed in previous studies in an episodic migraine population. The most common adverse events reported with a frequency ≥ 5% in at least one atogepant treatment arm, and greater than placebo, were constipation (10.0% for atogepant 60 mg QD, 10.9% for atogepant 30 mg BID, and 3.1% for placebo), and nausea (9.6% for atogepant 60 mg QD, 7.8% for atogepant 30 mg BID, and 3.5% for placebo). Most of the events of constipation and nausea were mild or moderate in severity. Most cases of constipation and nausea did not lead to discontinuation. There were no hepatic safety issues identified. Serious adverse events occurred in 2.7% of patients with atogepant 60 mg QD and 1.6 % of patients treated with atogepant 30 mg BID, compared to 1.2% of patients with placebo. None of these treatment-emergent adverse events were assessed as treatment-related by the investigator.

“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,” said Michael Severino, M.D., 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 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.”

These data build on the Phase 3 ADVANCE study results, which evaluated atogepant for the preventive treatment of episodic migraine.4 The primary endpoint of the Phase 3 ADVANCE study was a statistically significant reduction in mean monthly migraine days across the 12-week treatment period compared to placebo.

Based on the results of phase 3 PROGRESS trial in chronic migraine, AbbVie intends to submit a supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration for the expanded use of atogepant to include the preventive treatment of chronic migraine. Additionally, study results from the Phase 3 PROGRESS trial, along with the Phase 3 ADVANCE trial data, in episodic migraine, will form the basis for future regulatory submissions globally. Use of atogepant for the preventive treatment of chronic migraine in the United States is not approved and its safety and efficacy have not been evaluated by regulatory authorities. Use of atogepant for the preventive treatment of episodic migraine and chronic migraine outside of the United States is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

About the author

Avatar of Juergen T Steinmetz

Juergen T Steinmetz

Juergen Thomas Steinmetz has continuously worked in the travel and tourism industry since he was a teenager in Germany (1977).
He founded eTurboNews in 1999 as the first online newsletter for the global travel tourism industry.

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