AbbVie Submits Supplemental New Drug Application for Atogepant in Chronic Migraine

Originally approved for the preventive treatment of episodic migraine in Sept 2021, atogepant’s potential new indication stems from positive results from the double-blind, placebo-controlled, phase 3 PROGRESS trial.

Months after announcing positive phase 3 data, AbbVie has submitted a supplemental new drug application (sNDA) to the FDA to expand atogepant’s (Qulipta) indication to include the preventive treatment of chronic migraine. If approved, the medication would be the first oral calcitonin gene-related peptide (CGRP) receptor antagonist approved as a preventive treatment for both episodic and chronic migraine.1

Results from the PROGRESS trial (NCT03855137), a double-blind, placebo-controlled, parallel-group study assessing 60-mg once daily (QD) and 30-mg twice-daily (BID) doses of atogepant, were the basis for the submission. In that study, those in the 60-mg QD and 30-mg BID arms experienced statistically significant reductions of 6.88 and 7.46 in mean monthly migraine days (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; adjusted for multiple comparisons).2

"Having one oral medication to treat both episodic and chronic migraine would be an important advancement for health care providers and patients," Michael Gold, MD, therapeutic area head, Neuroscience Department, AbbVie, said in a statement. “This sNDA approval would also diversify AbbVie's migraine portfolio and make it the only company to offer two approved preventive treatments for those living with chronic migraine. No two migraine patients are alike, so having multiple treatment options with unique mechanisms of action is critical."1

Atogepant, originally approved in September 2021 as the first and only oral CGRP receptor for the preventive treatment of episodic migraine, continued to show a safe profile in PROGRESS as well. Constipation (60-mg QD: 10.0%; 30-mg BID: 10.9%; placebo: 3.1%) and nausea (60-mg QD: 9.6%; 30-mg BID: 7.8%; placebo: 3.5%) were among the most commonly reported (>5%) adverse events (AEs) in the trial. Most of these were mild or moderate in severity, and most cases did not lead to discontinuation. Serious AEs occurred in 2.7% of patients in the atogepant 60-mg QD group, 1.6% of those in the 30-mg BIG group, and 1.2% of those on placebo.2

In the modified intent-to-treat population (n = 755), achievement of 50% reduction in MMDs, a key secondary end point, was reported by 41.0% and 42.7% of patients, respectively, in the 60-mg QD and 30-mg BID atogepant arms, compared with 26% of those on placebo (all groups vs placebo, P ≤.0009). Results were similar in the European Union-focused off-treatment hypothetical estimate (OTHE) population (n = 760), with 40.1% and 42.1% of patients, respectively, in the atogepant treatment arms demonstrating this reduction, compared with 26.5% of those in the placebo group (all dose groups vs placebo, P ≤.0024).

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Atogepant’s original approval for episodic migraine was based off a clinical program that included almost 2000 patients treated with the medication, including those in the pivotal phase 3 ADVANCE study (NCT02848326). 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 (<.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.3

Recently, at the 2022 American Headache Society (AHS) Annual Meeting, June 9-12, in Denver, Colorado, post-hoc data from ADVANCE was presented and showed that atogepant was associated with dose-dependent decreases in body weight. After 12 weeks of treatment, patients on placebo demonstrated a least square mean percentage change in body weight of +0.37 compared with +0.14 (= 0.4138), –0.61 (= .0005), and –1.27 (<.0001), in the atogepant 10-, 30-, and 60-mg groups, respectively.4

REFERENCES
1. AbbVie submits supplemental new drug application to US FDA for atogepant (Qulipta) to support label expansion for the preventive treatment of migraine. News release. AbbVie. June 21, 2022. Accessed June 22, 2022. https://news.abbvie.com/news/press-releases/abbvie-submits-supplemental-new-drug-application-to-us-fda-for-atogepant-qulipta-to-support-label-expansion-for-preventive-treatment-migraine.htm
2. AbbVie announces positive phase 3 atogepant (Qulipta) data for preventive treatment of chronic migraine. News release. AbbVie. March 10, 2022. Accessed June 22, 2022. https://news.abbvie.com/news/press-releases/abbvie-announces-positive-phase-3-atogepant-qulipta-data-for-preventive-treatment-chronic-migraine.htm
3. Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the preventive treatment of migraine. NEJM. 2021; 385:695-706. doi:10.1056/NEJMoa2035908
4. Dodick DW, Hay DL, Walker CS, et al. Decrease in body weight with once-daily atogepant for the preventive treatment of migraine: a post hoc analysis. Presented at: AHS Annual Meeting, 2022; June 9-12; IOR-11