In the open-label extension where the highest dose of atogepant (Qulipta; AbbVie) was observed, 24.1% of participants had at least 7% weight loss compared with 14.7% of those on standard of care.
Atogepant (Qulipta; AbbVie), an oral, calcitonin gene-related peptide (CGRP) receptor antagonist FDA-approved for the prevention of migraine, was found to be associated with dose-dependent decreases in body weight, according to new post-hoc data from the phase 3 ADVANCE study (NCT02848326).1
Presented at the 2022 American Headache Society (AHS) Annual Meeting, June 9-12, in Denver, Colorado, the results showed a least square (LS) mean percentage change in body weight of +0.37 in the placebo group after 12 weeks compared with +0.14 (P = 0.4138), –0.61 (P = .0005), and –1.27 (P <.0001), in the atogepant 10-, 30-, and 60-mg groups, respectively. Atogepant is a relatively young drug within the field, gaining the FDA greenlight in September 2021 and becoming the second overall member of the gepant class to receive approval.
ADVANCE was a phase 3 trial that 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. Led by David W. Dodick, MD, professor of neurology, Mayo Clinic Scottsdale, the analysis presented at AHS 2022 specifically looked at LS mean percentage change in body weight and the proportion of participants with at least 7% change in body weight at any time point postbaseline.
In ADVANCE, 3.2% of those on placebo demonstrated at least 7% weight loss compared with 4.1%, 2.7%, and 5.7% for the atogepant 10-, 30-, and 60-mg groups, respectively. In contrast, weight gains of at least 7% were found in 2.3%, 1.8%, and 0.0% of those in the respective atogepant groups and 2.7% of those on placebo.
The analysis also included data from the open-label, 52-week extension, which randomized patients 1:1 to either standard of care or once-daily atogepant 60 mg. Here, Dodick et al observed LS mean percentage change of +0.19 for body fat after 52 weeks on standard of care vs –1.57 for those in the highest dose atogepant group (P =.0003). In comparison, 14.7% of those on standard of care had at least 7% weight loss compared with 24.1% of those on atogepant 60 mg. Weight gains of at least 7% were observed in 12.6% and 7.3% of those on standard of care or atogepant 60 mg, respectively.
After the American Academy of Neurology Annual Meeting, April 2-7, 2022, where similar results from ADVANCE were also presented, NeurologyLive® spoke with Jessica Ailani, MD, director, MedStar Georgetown Headache Center, on the Mind Moments™ podcast, about these data. Ailani, who presented the data at AHS 2022, noted that the body weight decrease observed not usually a concern for women, who make up the majority of patients with migraine. She called the results surprising, but good, news.
"We don't really have any other preventive treatment that does this outside of topiramate, and most of the time, patients are coming in asking for anything that doesn't cause weight gain. They say, ‘as long as it doesn't cause weight gain, I'm going to be okay with it,’” she said. “Just to give us a frame of reference, about 10% of people will lose about 10% of their body weight on topiramate. That's the average that we're looking at, with a similar preventive medication treatment regimen, for people for with migraine. In patients who are starting atogepant, at 60 mg daily for migraine prevention, we tell them that they can have a decrease of body weight, but that is usually a small amount of body weight. It's also important to realize that this was seen across the spectrum. If a person was on the smaller side or on had a larger BMI where they could lose weight, and then the longer they were on it, the more likely they would lose weight."
Ailani noted that the individuals who were on atogepant for 52 weeks were more likely to lose slightly more weight than those that remained on it only for 3 months. She said that the underlying process for this weight loss was still being investigated, as it did not appear to be correlated with response or the CGRP-focused mechanism of action.
"I think this is a fascinating area, and personally, for someone who's a clinician very interested in science, this just shows us that these drugs do have other targets, especially the oral agents, and that's probably might have some meaning and how they're working for migraine as well,” Ailani said. “It's really opened up this whole area of, ‘Oh my goodness, look, there's something else going on.’ What does that actually mean about this drug, and what else it could possibly be doing? Is this something that's unique to atogepant, or are we going to see it with other products? It wasn't seen with rimegepant, but that is dosed every other day. So, is it unique to dosing? Is it unique to dosing regimen? We may see it with other future gepants, so I think it's something for us to watch."
In the original ADVANCE analysis, 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). 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.2
Although approved for episodic migraine, the preventive recently met its primary end point in a phase 3 study evaluating patients with chronic migraine (CM). Data from the PROGRESS trial (NCT03855137) showed that those on 60-mg once-daily and 30-mg twice daily of atogepant experienced decreases of 6.88 and 7.46 in monthly migraine days (MMD), respectively, compared with patients in the placebo arm, who had a decrease of 5.05 MMDs (60 mg QD vs placebo; P = .0009; 30 mg BID vs placebo, P <.0001). AbbVie noted that they intend to submit a supplemental new drug application to the FDA for the expanded use of atogepant to include the preventive treatment of CM.3