A 52‐week open‐label extension study to evaluate the safety and efficacy of oral rimegepant for the preventive treatment of migraine

Abstract Objective To assess the safety, tolerability, and treatment effects of rimegepant 75 mg every other calendar day (EOD) for the preventive treatment of migraine in a 52‐week, open‐label extension (OLE) study. Background Rimegepant is an oral small molecule calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine and the preventive treatment of episodic migraine in adults. The efficacy and safety of rimegepant for preventive treatment of migraine was demonstrated in a 12‐week, phase 2/3, randomized, double‐blind (DB), placebo‐controlled trial in which rimegepant treatment produced significant improvement in the number of monthly migraine days (MMDs) with a safety profile similar to placebo. Methods In the DB trial period, an initial 4‐week observation period was followed by a randomized, DB, 12‐week treatment period. This was an optional 52‐week OLE following the initial DB study for adults who completed the DB period. Participants were instructed to take one tablet of rimegepant 75 mg EOD for 52 weeks. If participants required an acute treatment of migraine on a non‐scheduled dosing day, they could take one tablet of rimegepant 75 mg on that day (as‐needed dosing). Secondary endpoints evaluated the safety and tolerability of rimegepant, including the frequencies of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3× upper limit of normal (ULN) concurrent with total bilirubin (TBIL) > 2× ULN, hepatic‐related adverse events (AEs), and hepatic‐related AEs leading to rimegepant discontinuation. Exploratory endpoints included the mean reduction in the number of MMDs. The study (DB and OLE) was conducted from November 2018 to February 2021. Results Of 603 participants who entered the OLE period, 428 (71.0%) completed the study. Overall, 312 (51.7%) participants reported at least one on‐study AE and most events were mild in severity. Severe AEs were reported in 14 (2.3%) participants. Serious AEs were reported in 13 participants (2.2%); none were liver related. AEs considered related to rimegepant were reported in 91 (15.1%) participants; the most frequently reported were constipation ( n = 6, 1.0%), upper respiratory tract infection ( n = 5, 0.8%), nausea, migraine, ALT increased, AST increased, and weight increased ( n = 4, 0.7% each). Hepatic‐related AEs occurred with low frequency ( n = 11, 1.8%). AEs leading to rimegepant discontinuation were also uncommon ( n = 17, 2.8%); two (0.3%) discontinued due to liver enzyme–related AEs. No participant had ALT or AST > 3× ULN concurrent with TBIL > 2× ULN. Over the OLE period, there was a mean (standard deviation) decrease of 6.2 (3.81) days in the number of MMDs. Mean MMDs and participants achieving categorical response rates improved over the OLE period, without any evidence of a diminution of effect. Conclusions The OLE data showed favorable tolerability and sustained and increasing treatment benefits with rimegepant 75 mg (EOD and as‐needed dosing) over 52 weeks for the preventive treatment of migraine. NCT03732638.