Atogepant well-tolerated, linked to significant migraine reduction

Key takeaways:

• Researchers examined more than 300 adults with episodic migraine who failed two to four conventional treatments.
• Treatment-emergent adverse events were minimal.

Treatment with atogepant was safe, effective and well-tolerated over 12 weeks in those with episodic migraine who failed multiple conventional therapies, with significant reductions in mean monthly migraine days compared with placebo.

“Among people with episodic migraine, 27% experience more than 3 headache days per month,” Cristina Tassorelli, MD, a professor in the department of brain and behavioral science at the University of Pavia in Italy, and colleagues wrote The Lancet Neurology. “Scientific and expert consensus is generally that treating physicians should consider initiating preventive treatment when migraine attacks are severely disabling.”

Tassorelli and colleagues sought to evaluate safety, efficacy and tolerability of atogepant for episodic migraine in adults who had failed to respond to two to four classes of conventional oral preventive treatments.

The randomized, double-blind, placebo-controlled, parallel-group, phase 3b ELEVATE clinical trial was conducted at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the United Kingdom and the United States. From an initial cohort of 540 individuals, 313 participants (89% female, 96% white) were assigned on a 1:1 basis to either 60 mg atogepant once a day or placebo for 12 weeks, with treatment population stratified by baseline monthly migraine days, number of treatment classes participants have been failed by and geographic region. In addition, 309 participants in the off-treatment hypothetical estimand (OTHE) population were randomized 1:1 to receive the same.

The primary endpoint was change from baseline in mean monthly migraine days through week 12, including the safety population (all who received at least one dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods either on or off treatment.

In the OTHE population, results showed that least squares mean changes from baseline were 1.9 (SE 0.4) with placebo and 4.2 (0.4) with atogepant (least squares mean difference 2.4, 95% CI: 3.2 to 1.5).

The most common treatment-emergent adverse event was constipation, while serious adverse events occurred in four of 156 participants in the atogepant group compared with none in the placebo group. Treatment-emergent adverse events resulting in discontinuation occurred in three participants in the atogepant group and two in the placebo group.

“This is, to our knowledge, the first study for an oral, small molecule [calcitonin gene-related peptide] receptor antagonist to show high efficacy, safety and tolerability for this difficult-to-treat population,” Tassorelli and colleagues wrote.