Phase 3 PROGRESS Results Highlight Atogepant’s Benefit in Chronic Migraine

Author(s):

In comparison with placebo, atogepant 30 mg twice daily and 60 mg once daily resulted in greater reductions in monthly migraine days, as well as proportion of patients with at least 50% reduction in 3-month average of MMDs.

Patricia Pozo-Rosich, MD, PhD

Weeks after the FDA expanded the indication for atogepant (Qulipta; AbbVie) to include the treatment of chronic migraine, findings presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts, further supported its efficacy.

The data presented was from the phase 3 PROGRESS study (NCT03855137), a 12-week trial that was the basis for the expanded indication. Led by Patricia Pozo-Rosich, MD, PhD, a professor of neurology and head of the Neurology Section at Vall d'Hebron Hospital and Institute of Research, in Spain, PROGRESS included 778 individuals with chronic migraine who were randomly assigned to either atogepant 30 mg twice daily (BID), 60 mg once daily (QD), or placebo. Like many migraine studies, the primary end point was change from baseline in mean monthly migraine days (MMDs), with proportion of patients experiencing at least 50% reduction in 3-month average of MMDs as the secondary end point.

As baseline, the mean MMDs in the modified intent-to-treat (mITT) population (n = 755) were 18.6-19.2 across groups. At the end of the 12-week treatment period, patients on atogepant 30 mg BID and 60 mg QD experienced mean change in MMDs of –7.5 and –6.9 days, respectively, compared with changes of –5.1 for those on placebo (30 mg BID vs placebo: P <.0001; 60 mg BID vs placebo; P = .0009). 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).

In terms of safety, treatment-emergent adverse events (TEAEs) were reported by 56.4%, 63.2%, and 49.4% of patients in the atogepant 30 mg BID, atogepant 60 mg QD, and placebo groups, respectively. Constipation, occurring in 10.9%, 10.0%, and 3.1% of those on atogepant 30 mg BID, 60 mg QD, and placebo, respectively, was the most frequent TEAE, followed by nausea (atogepant 30 mg BID: 7.8%; 60 mg QD: 9.6%; placebo: 3.5%). Serious TEAEs were reported by 1.6% of patients on atogepant 30 mg BID, 2.7% on atogepant 60 mg QD, and 1.2% of patients on placebo. None of them were considered treatment-related.

A second presentation from PROGRESS assessed the safety of atogepant in individuals with cardiovascular disease risk factors (CV-RFs). Patients in the treatment groups were stratified into 1 of 3 CV-RF groups (0, 1, or ≥2 CV-RFs) based on current presence or history of CV-RFs. Outcomes included descriptive demographics and baseline characteristics, the most common CV-RFs, and cardiovascular treatment-emergent adverse events (CV-TEAEs).

Results showed that the most common CV-RFs, occurring in more than 10% of patients in PROGRESS (n = 773), were dyslipidemia (47.6%), followed by body mass index greater than 25 kg/m2 (43.1%), hypertension (40.9%), and age (18.9%). Other CV-RFs included CVD/diabetes medication (3.1%), diabetes (2.5%), sleep apnea (2.1%), history of stroke/myocardial infarction/transient ischemic attack/peripheral vascular disease (0.6%), and smoking (0.1%).

Among all participants, the majority had at least 2 CV-RFs compared to either 0 or 1 CV-FV. Only 1 CV-TEAE of palpitations in the atogepant 30 mg BID group led to treatment discontinuation. Few CV-TEAEs were considered treatment-related (n = 4) and none of these led to treatment discontinuation. In the pooled atogepant groups, 50.4% had at least 2 CV-RFs, 28.1% had 1, and 21.2% had 0. In comparison, 45.5%, 36.1%, and 18.4% of patients in the placebo group had at least 2, 1, or 0 CV-RFs.

Atogepant is available in 3 doses for the preventive treatment of episodic migraine: 10 mg, 30 mg, and 60 mg; however, only the 60-mg dose was indicated for the preventive treatment of chronic migraine.

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REFERENCES
1. 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.
2. Best P, Harriott A, Monteih T, et al. Post hoc analysis of PROGRESS: evaluating the safety and efficacy of atogepant in participants with chronic migraine and cardiovascular risk factors. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstract 8189