Migraine Preventative Atogepant Met Phase 2b/3 Primary Endpoint

David Nicholson, PhD

Today, Allergan announced positive topline results from CGP-MD-01, a phase 2b/3 clinical trial of atogepant. All active treatment arms met the primary endpoint of a statistically significant reduction from baseline in monthly migraine/probable migraine (MPM) headache days in patients treated with atogepant compared with placebo.

“What these data, coupled with the data from ubrogepant, mean is that for the first time we have a mechanism of action that demonstrated efficacy and safety for both the treatment and prevention of migraine,” David Nicholson, PhD, Chief Research and Development Officer, Allergan told MD Magazine.

The migraine prophylaxis was tested as a daily or twice-daily treatment for patients with episodic migraine. Other migraine preventatives currently being studied, such as galcanezumab and fremanezumab, are injected on a monthly or quarterly basis.

Nicholson noted that many patients would prefer to swallow a pill rather than receive an injection, even if the pill is more frequent. He added that the daily regimen also allows physicians and patients to quickly stop treatment, should that become necessary, while monthly or quarterly treatments remain in the patient’s system much longer.

Atogepant is an oral investigational calcitonin gene-related peptide (CGRP) receptor antagonist. In the CGP-MD-01 study, 834 patients were randomized (2:1:2:1:2:1) to placebo (n = 178), 10-mg QD (n = 92), 30-mg QD (n = 182), 30-mg BID (n = 79), 60-mg QD (n = 177), and 60-mg BID (n = 87), respectively, and treated under double blind conditions 12 weeks.

The study encompassed a 4-week screening period to determine baseline migraine frequency as well as a 4-week safety follow-up period. Participants included adults 18 to 75 years of age (mean age 40.1 years) with at least a 1-year history of migraine with or without aura. Eligible patients experienced between 4-14 migraine/probable migraine (MPM) headache days per month on average in the 3 months prior to beginning the study and during the 4-week baseline period.

Across the 12-week treatment period, patients treated with atrogepant experienced greater reductions in mean MPM headache days compared to placebo [placebo -2.85 (SE 0.23); 10 mg QD -4.00 (0.32); 30 mg QD -3.76 (0.23); 60 mg QD -3.55 (0.23); 30 mg BID -4.23 (0.35); 60 mg BID -4.14 (0.33)].

The best-performing treatment arm, 30 mg of atogepant BID, saw a change of -4.23 MPM headache days from baseline. This arm had a least square mean difference of -1.39 (SE 0.42) compared to placebo.

“These exciting results demonstrate the potential for atogepant for a broad spectrum of migraine patients. The efficacy and safety across doses and dose regimens show promise in a patient population with high unmet treatment needs,” said Peter Goadsby, MD, PhD, DSc,

Neurologist and Professor at Kings College, London and University of California, San Francisco. “Results from this atogepant trial provide continued evidence for the clinical potential of oral CGRP antagonists and the substantial value of progressing research and developing new treatments for migraine patients.”

The CGP-MD-01 trial results showed that atogepant was well tolerated and safe, across all doses.

“The data that we reported today were very exciting data, because they showed that this oral agent is not only efficacious, but in this study, it is safe. The effects on liver toxicity were placebo-like,” said Nicholson. He emphasized that there has been no indication of hepatoxicity and that atogepant has proven safe in animal and all clinical trials to date.

The most common adverse events in the trial, occurring with a frequency >5% in at least 1 treatment arm and greater than placebo, were nausea, fatigue, constipation, nasopharyngitis, and urinary tract infection.

“The positive results from this study show that oral atogepant has a compelling profile relative to other treatment options on the market and in development for the prevention of migraine. We are excited about the prospects for this product and rapidly moving to the next stage of development,” said Bill Meury, Chief Commercial Officer at Allergan.

The company plans to proceed with its phase 3 program for atogepant after discussions with regulatory agencies.

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