Atogepant Reduces Monthly Migraine Days in Patients With Chronic Migraine

Atogepant is effective in reducing the number of mean monthly migraine days (MMDs) among patients with chronic migraine, according to study findings published in the journal the Lancet.

There is limited research regarding oral preventative generic migraine medications and their effects on chronic migraine, specifically for small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists. Researchers conducted a study to assess the efficacy, safety, and tolerability of the preventive use of atogepant in patients with chronic migraine. 

The PROGRESS study (ClinicalTrials.gov Identifier: NCT03855137) was a phase 3, multicenter, randomized, double-blinded trial conducted in 142 international research sites. 

Study participants were aged 18-80 years with chronic migraine for at least 12 months. Chronic migraine was classified according to the International Classification of Headache Disorders, third edition (ICHD-3) and defined as at least 15 headache days in a month for at least 3 months before baseline screening. Headache onset was required to occur before age 50. 

They were randomly assigned to receive atogepant 30 mg twice daily, 60 mg once daily, or a placebo regimen for 12 weeks. Study participants were assigned certain regimens based on their previous exposure to migraine medications and region.

The participants were permitted to use acute migraine medications when necessary, except for CGRP antagonists. The primary endpoint was the change in mean MMDs from the start of the study to the end of the 12-week treatment period. 

A total of 1489 participants were screened for eligibility and 711 were excluded from the final analysis. Of the 778 remaining participants, 357 were assigned to receive atogepant 30 mg twice a day, 262 to atogepant 60 mg once a day, and 259 to the placebo regimen. The age range of participants was 18 to 74 (mean age, 42.1) years, 677 (88%) of the 773 patients were women, and 459 (59%) of participants were White. 

The safety population included 773 (99%) of 778 participants and 755 were included in the modified intention-to-treat (mITT) population. 

The changes in MMDs from baseline were -7.5 for atogepant 30 mg twice a day (standard error [SE], 0.4), -6.9 for atogepant 60 mg once a day (SE, 0.4), and -5.1 for placebo (SE, 0.4).

The adjusted least squares mean differences (LSMDs) from placebo to each investigational group were -2.4 days for atogepant 30 mg twice a day (95% CI, -3.5 to -1.3; P <.0001) and -1.8 days with atogepant 60 mg once a day (95% CI, -2.9 to -0.8; P =.0009).

A total of 4 (2%) out of 257 participants taking atogepant 30 mg twice daily, 7 (3%) of 261 participants taking atogepant 60 mg once daily, and 3 (1%) of 255 patients on the placebo regimen reported a serious adverse event (AE). 

The most reported AEs were constipation and nausea. The researchers also noted significant weight decreases in 6% of patients taking atogepant 30 mg twice a day 14, 6% for atogepant 60 mg once a day 15, and 2% for placebo.

“These findings extend the benefits of atogepant to chronic migraine, making it the first CGRP-targeted, efficacious, and well tolerated oral preventive treatment option for individuals with chronic migraine,” the researchers noted.

Study limitations included short treatment duration and the inability to determine long-term AEs.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.