A 156-week safety extension study presented at EAN 2026 shows the first 3-year long-term results for atogepant in the preventive treatment of migraine in individuals with chronic migraine (CM) or episodic migraine (EM) who had an insufficient response to 2–4 classes of conventional oral, non-migraine-specific preventive migraine treatments.
At the lead-in study baseline, the mean scores in the Activity Impairment in Migraine–Diary (AIM–D) performance of daily activities (PDA) domain were 31.6, 18.9, and 25.6 in the PROGRESS, ELEVATE, and total cohorts, respectively. The corresponding physical impairment (PI) domain scores were 27.2, 15.6, and 21.7. For the Migraine-Specific Quality of Life Questionnaire v2.1 Role–Function Restrictive (MSQv2.1 RFR) domain, the mean scores were 40.7, 43.1, and 41.8.
At week 13–16 of the open-label extension (OLE) period, treatment with atogepant led to a reduction (ie, improvement) in the AIM–D PDA domain score (mean change from baseline [CFB], –19.7, –12, and –16 for the PROGRESS, ELEVATE, and total cohorts, respectively), which persisted through week 153–156 (mean CFB, –20.5, –13.4, and –16.3, respectively).
This pattern was similarly seen for the AIM–D PI domain score across the PROGRESS, ELEVATE, and total cohorts (week 13–16: mean CFB, –16.5, –9.7, and –13.2, respectively; week 153–156: mean CFB, –16.8, –10.9, and –13.4).
Atogepant treatment also led to an improvement (mean increase from baseline) in the MSQv2.1 RFR domain score at week 12 of the OLE period (mean CFB, 32.3, 37.5, and 34.7 for the PROGRESS, ELEVATE, and total cohorts, respectively), which was sustained through week 156 (mean CFB, 35.3, 38.1, and 36.7). The investigators noted that these translated to improvements in social and work-related activities.
“Moreover, the safety profile in this OLE study was consistent with the known safety profile of atogepant. No new safety signals were observed,” the investigators said.
First oral CGRP for EM and CM
Atogepant is the first oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for the preventive treatment of both EM and CM. [Drugs 2022;82:65-70; Lancet 2023;402:748-749] “Long-term evaluation of treatments is critical for the management of migraine,” the researchers said.
This phase III, long-term safety extension study included adults with CM or EM who had an inadequate response to 2–4 classes of conventional oral preventive treatment and had completed the lead-in phases of the PROGRESS or ELEVATE studies, respectively. The participants received atogepant 60 mg QD. [Lancet 2023;402:775-785; Lancet Neurol 2024;23:382-392]
PROGRESS completers had ≥15 monthly headache days, including ≥8 meeting criteria for migraine at PROGRESS baseline. [EAN 2026, abstract EPO-0315]
ELEVATE completers had 4–14 monthly migraine days at ELEVATE baseline, who had insufficient response to 2–4 classes of conventional oral non-migraine-specific preventive migraine treatments. Some participants had a gap between the lead-in study and OLE, during which they were off atogepant.
The modified intention-to-treat population comprised 529 participants (PROGRESS: n=285; ELEVATE: n=244). Of these, 376 (n=185 and 191, respectively) completed the 3-year OLE treatment period. The mean age was 42 years, approximately 88 percent of the participants were women, and 11.4 percent were from East Asia.