Long-Term Atogepant Effective, Safe as Migraine Preventive, Open-Label Studies Show

At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, AbbVie presented new interim data from an ongoing open-label study of 2 phase 3 trials assessing atogepant (Qulipta) as a preventive medication in patients with episodic or chronic migraine. All told, over a 156-week treatment period, the therapy maintained a safety profile that was consistent with its known profile, as well as demonstrated impacts on other efficacy outcomes such as acute medication use days.¹

Otherwise known as Study 3101-312-002 (NCT04686136), the trial includes 595 patients who received at least 1 dose of atogepant from either the phase 3 PROGRESS (NCT03855137) or ELEVATE (NCT04740827) trials. The modified intention-to-treat population included participants who received at least 1 dose of atogepant and had at least 1 evaluable post-baseline 4-week period of eDiary data (n = 524). The current interim analysis was performed after all study participants completed the efficacy data collection portion of the study at week 52 or early termination.

At the interim analysis, monthly migraine days (MMDs) improved on average by 8.5 days at weeks 13-16, which was consistent over 48 weeks. AbbVie noted that similar improvements were seen in monthly headache days and monthly acute medication use days. At a dose of 60 mg, atogepant had a safety profile that was similar to previous trials, with no new signals observed. Treatment with the calcitonin gene-related peptide (CGRP) antagonist resulted in a reduction of at least 50% in monthly migraine days during weeks 13-16 for 70% of individuals in the study.

"Migraine is a debilitating neurological disease that can have a significant impact on day-to-day life,” lead investigator Sait Ashina, MD, assistant professor of neurology and anesthesia at Harvard Medical School, director of the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston, said in a statement.¹ "As the first report of one-year atogepant data in patients with chronic migraine, this builds on the long-term observed safety and efficacy in the episodic migraine population and demonstrates atogepant's ability to reduce migraine days and acute medication use across the spectrum of the disease."

The 50% or more reductions in monthly migraine days were also consistent throughout the 48 weeks of open-label treatment. Among the common treatment-emergent adverse events observed, the most common were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

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Atogepant, a CGRP-targeting medication, originally received FDA approval as a preventive for episodic migraine in September 2021, and had its label expanded to include chronic migraine earlier this year. In August 2023, the European Commission approved atogepant as a treatment for adults with 4 or more migraine days per month, becoming the first and only CGRP agent indicated for prevention of both episodic and chronic migraine. The approval was based on PROGRESS and another phase 3 study, ADVANCE (NCT02848326), in which atogepant-treated patients showed greater reduction of monthly migraine days than placebo.²

"We understand that migraine is a complex disease and AbbVie is steadfast in our commitment to alleviating the considerable burden facing migraine patients," Dawn Carlson, vice president of Neuroscience Development at AbbVie, said in a statement.¹ "Patients should accept nothing less than migraine freedom, and the long-term safety and efficacy shown in this interim analysis marks another step toward that goal."

In the original PROGRESS study, those in the 60-mg QD and 30-mg BID arms of atogepant experienced decreases of 6.88 MMDs and 7.46 MMDs, 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). Reduction of at least 50% in 3-month average of MMDs was achieved by 42.7% of participants in the atogepant 30 mg BID group, 41.0% in the atogepant 60 mg QD group, and 26.0% in the placebo group (30 mg BID vs placebo: P = .0003; 60 mg QD vs placebo; P = .0009).³

In ELEVATE, most patients (77%) had between 8 and fewer than 15 monthly migraine days. Most participants reported failure by 2 classes of previous preventive treatments (56%), whereas 35% had been failed by 3, and 9% of the cohort had been failed by 4. Results at 12 weeks showed a least square mean (LSM) change of –4.2 (SE, 0.4) monthly migraine days with atogepant vs –1.9 (SE, 0.4) on placebo (adjusted P <.0001). Atogepant continued to outperform placebo in a number of secondary outcomes, including reduction of at least 50% in the 3-month average of mean monthly migraine days (51% vs 18%; OR, 4.8; 95% CI, 2.9-8.1; P <.0001) and mean monthly acute medication use days (–3.7 [SE, 0.4] vs –1.1 [SE, 0.4]; P <.0001).⁴

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REFERENCES
1. AbbVie announces late-breaking data at AAN supporting long-term safety and efficacy of atogepant (Qulipta) for preventive treatment of migraine. News release. AbbVie. April 12, 2024. Accessed April 13, 2024. https://news.abbvie.com/2024-04-12-AbbVie-Announces-Late-Breaking-Data-at-AAN-Supporting-Long-Term-Safety-and-Efficacy-of-Atogepant-QULIPTA-R-for-Preventive-Treatment-of-Migraine
2. AbbVie announces European Commission approval of Aquipta (atogepant) for the preventive treatment of migraine in adults. News release. AbbVie. August 17, 2023. Accessed April 13, 2024. https://news.abbvie.com/news/press-releases/news-type/rd-news/abbvie-announces-european-commission-approval-aquipta-atogepant-for-preventive-treatment-migraine-in-adults.htm
3. Pozo-Rosich P, Ailani J, Ashina M, et al. Atogepant for the preventive treatment of chronic migraine: results from the PROGRESS phase 3 trial. Presented at: 2023 AAN Annual meeting; April 22-27; Boston, MA. Abstract 003980.
4. Tassorelli C, Nagy K, Pozo-Rosich P, et al. Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial. Lancet Neurol. Published online February 13, 2024. doi:10.1016/S1474-4422(24)00025-5.