Atogepant 60 mg Demonstrates Superior to Placebo for Migraine by Day 1

Richard B. Lipton, MD

Credit: Albert Einstein College of Medicine

An analysis of 3 preventive studies showed that 4 weeks of treatment with atogepant 60 mg for migraine demonstrated superiority over placebo in efficacy and functional measures.¹

“Migraine is the second-leading cause of disability in the overall population and the leading cause of disability in young women, with people reporting negative effects on their relationships, parenting, career, and finances,” said lead investigator Richard B. Lipton, MD, of Albert Einstein College of Medicine in the Bronx, New York, and a fellow of the American Academy of Neurology, in a statement.² “Having a treatment that can act quickly and effectively addresses a key need.”

The study, published in Neurology, the medical journal of the American Academy of Neurology, analyzed 3 phase 3, multicenter, randomized, double-blind, placebo-controlled 12-week trials called ADVANCE, ELEVATE, and PROGRESS which had demonstrated the efficacy and safety of atogepant, an oral calcitonin gene-related peptide receptor antagonist, in episodic migraine and chronic migraine.¹ All 3 trials included participants aged 18 – 80 years. The study’s population included participants from the studies ADVANCE (atogepant, n = 222; placebo, n = 214), ELEVATE (atogepant, n = 151; placebo, n = 154), and PROGRESS (atogepant, n = 256; placebo, n = 246).

In ADVANCE and ELEVATE, participants had > 1 year history of episodic migraine and 4 – 14 migraine days. Participants in ELEVATE needed previous treatment failures to 2 – 4 classes of oral preventives. Moreover, PROGRESS included participants with > 1 year of chronic migraine, ≥ 15 monthly headache days, and ≥ 8 monthly migraine days. People with episodic migraines experience ≥ 14 migraine days per month, and people with chronic migraine experience ≥ 15 days of headache per month, with ≥ 8 having migraine characteristics.

The study’s efficacy endpoints included change from baseline to week 4 in weekly and monthly migraine days, and functional endpoints included scores of Activity Impairment in Migraine-Diary at weeks 1 – 4 and the European Quality-of-Life 5-Dimension 5-Level at weeks 1 – 2 and 4.

The study found participants on atogepant were less likely to have a migraine on the first day of taking the drug compared to those taking a placebo, as seen in ADVANCE (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.23 – 0.67; P = .0006), ELEVATE (OR, 0.53; 95% CI, 0.29 – 0.94; P = .031), and PROGRESS (OR, 0.63; 95% CI, 0.43 – 0.93; P = .021). On day 1, the percentage of participants who had a migraine was 12% on atogepant versus 25% on placebo; the numbers for ELEVATE and PROGRESS were 15% versus 26% and 51%, and 61%, respectively.

After adjusting for factors that could affect the migraine rate, the study showed people taking the drug were 61% less likely to have a migraine in ADVANCE, 47% less likely in ELEVATE, and 37% less likely in PROGRESS.

Participants on atogepant also had fewer weekly migraines during weeks 1 – 4 and improved Activity Impairment in Migraine-Diary and the European Quality-of-Life 5-Dimension 5-Level during weeks 1 – 4 compared with placebo.

ADVANCE and ELEVATE revealed that people taking atogepant had an average of 1 fewer day with migraine per week, compared with an average of < ½ day fewer per week among those taking placebo. In PROGRESS, the average migraine days per week were reduced by approximately 1.5 days for participants on atogepant compared with approximately 1 day for participants on placebo.

Investigators wrote how the findings of this study were limited by a sample of mostly female and White participants, so the results may not be generalizable to other populations.

“With many current drugs to prevent migraine, it takes time to find the right dosage for the individual and it can take weeks or even months for it to be most effective,” Lipton said.² “Some people give up and stop taking the drugs before they reach this point. Plus, many people experience side effects with current treatments. Developing a drug that works both effectively and quickly is critical.”

References

1. ^{Lipton RB, Gandhi P, Tassorelli C, Reuter U, Harriott AM, Holle-Lee D, Gottschalk CH, Neel B, Liu Y, Guo H, Stokes J, Nagy K, Dabruzzo B, Smith JH. Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials. Neurology. 2025 Jan 28;104(2):e210212. doi: 10.1212/WNL.0000000000210212. Epub 2024 Dec 23. PMID: 39715475.}
2. ^{New drug to prevent migraine may start working right away. EurekAlert! December 23, 2024. https://www.eurekalert.org/news-releases/1068984?. Accessed December 24, 2024.}