The gepant, marketed as Qulipta, is the first oral calcitonin gene-related peptide receptor antagonist approved for episodic migraine.
The FDA has approved AbbVie’s atogepant (Qulipta) for the preventive treatment of episodic migraine in adult patients, making it the first oral calcitonin gene-related peptide (CGRP) receptor antagonist—known colloquially as gepants—for this specific indication.1 It joins rimegepant (Nurtec ODT; Biohaven) as the second overall member of the gepant class to receive FDA approval.
The decision was made based on data from a clinical program evaluating the efficacy, safety and tolerability of atogepant in almost 2000 patients with episodic migraine, defined as 4 to 14 migraine days per month. One of the studies, the pivotal phase 3 ADVANCE study (NCT02848326), included 873 patients with episodic migraine 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
"Millions of people living with migraine often lose days of productivity each month because attacks can be debilitating. Qulipta can help by reducing monthly migraine days with a once-daily, oral dose that works quickly and continuously," Michael Severino, MD, vice chairman and president, AbbVie, said in a statement.1 "We are proud that AbbVie is now the only pharmaceutical company to offer three products across the full spectrum of migraine treatment, which include preventive therapies for chronic and episodic migraine and an acute treatment for migraine attacks."
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).2 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.
Additional results showed that treatment with the agent met primary end point, with decreases in mean monthly headache days of 3.7, 3.9, and 4.2 days, respectively, in the 10 mg (n = 214), 30 mg (n = 223), and 60 mg (n = 222) atogepant groups compared with a 2.5-day decline in the placebo arm.3
"Atogepant provides a disease specific option for migraine prevention that is effective and well-tolerated in clinical trials. With FDA approval, clinicians will now have the opportunity to see where atogepant may seperate from other therapies in practice and, hopefully, the field will take another step towards migraine freedom," Jessica Ailani, MD, FAHS, director, MedStar Georgetown Headache Center, and investigator in the atogepant clinical trials, told NeurologyLive.
ADVANCE also revealed a change of –3.7, –3.7, and –3.9 in the mean number of days of use of medication to treat migraine attacks per month from baseline that was reported across all 3 treatment groups, compared with –2.4 for placebo (P <.001 for all comparisons with placebo). A reduction of 50% or more in the 3-month average of migraine days was reported by 55.6% of participants in the 10-mg atogepant group, 58.7% of those in the 30-mg group, 60.8% of those in the 60-mg atogepant group, and 29% for those in the placebo group (P <.001 for all comparisons with placebo).2
For both the 30-mg and 60-mg dose groups, investigators observed significantly greater score improvements of –2.5 points (P = .0005) and –3.3 points (P <.0001) in the mean monthly AIM-D Performance of Daily Activities domain. Similarly, patients in these dose groups also showed statistically greater improvement in the Physical Impairment domain in the AIM-D score (30-mg atogepant, –2.0 [P = .0021]; 60-mg atogepant, –2.5 [P = .0002]). On the other hand, those in the 10-mg atogepant group did not have significant differences on the Performances of Daily Activities domain of the AIM-D (difference, –1.2 [95% CI, –2.6 to 0.2]) and the score on the Physical Impairment domain of the AIM-D (difference, –1.1 [95% CI, –2.3 to 0.1).
"This approval reflects a broader shift in the treatment and management paradigm for the migraine community. Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients," Peter J. Goadsby, MD, PhD, DSc, neurologist and professor, University of California–Los Angeles, and King's College, London, and co-author of the ADVANCE study, said in a statement.1 "I'm particularly encouraged by the convenience of the oral daily use of QULIPTA, its rapid onset of significant efficacy, and its safety and tolerability as well as its high patient response rates. This is a milestone in preventive migraine treatment that I hope will help many patients for years to come.”
Results from an open-label extension trial evaluating atogepant 60-mg showed that the treatment sustained efficacy in reducing monthly migraine days (MMDs), moderate/severe headache days, and acute medication use days over the 1-year study period. Lead author of that study, Messoud Ashina, MD, PhD, DMSc, director, Human Migraine Research Unit, Danish Headache Center, and colleagues presented these findings at the 2021 Virtual American Headache Society (AHS) 63rd Annual Scientific Meeting. Participants with 4-14 migraine days per month included in the study were randomized 5:2 to atogepant 60 mg once daily (n = 500) or oral standard of care (n = 200) migraine preventive medication. Eligible participants had completed the phase 2b/3 trial (NCT02848326) or were newly enrolled in the current trial.4