P.030 Long-term Safety and Tolerability of Atogepant 60 mg Following Once-Daily Dosing Over 1 Year for the Preventive Treatment of Migraine

Abstract

Background: The goal of the study was to assess the safety and tolerability of atogepant, an oral, calcitonin gene-related peptide receptor antagonist in development for migraine preventive treatment, once daily over 1 year. Methods: Multicenter, open-label trial (NCT03700320). Adults with migraine were randomized 5:2 to atogepant or oral standard-of-care (SOC) migraine prevention. Results: 744 randomized participants (n=546 atogepant), 739 safety population participants (n=543 atogepant). Adverse events (AEs) were reported by 67.0% of atogepant participants; 18.0% had AEs considered related to atogepant. AEs reported by ≥5% of atogepant-treated participants were upper respiratory tract infection (10.3%), constipation (7.2%), nausea (6.3%), and urinary tract infection (5.2%). 4.4% of atogepant participants reported serious AEs that included various, common medical conditions; no event occurred in ≥1 participant and none were atogepant-related. Two deaths were reported in atogepant-treated participants (homicide victim; toxic shock syndrome); both were considered not treatment-related. 5.7% of atogepant participants discontinued due to AEs. Alanine aminotransferase/aspartate aminotransferase levels ≥3X upper limit of normal were reported for 2.4% of atogepant participants (n=13/531) and 3.2% of SOC participants (n=6/190). No cases of potential Hy’s Law were reported. Conclusions: Once-daily use of atogepant for preventive treatment of migraine over 1 year was safe and well-tolerated with no safety concerns identified.

Atogepant for the Prevention of Episodic Migraine in Adults: A Systematic Review and Meta-Analysis of Efficacy and Safety

“…The 12-week treatment duration is not adequate to assess the long-term efficacy and side effects of atogepant. In this regard, atogepant 60 mg administered once daily to patients with episodic migraine over a 52-week open-label, multicenter, phase III extension study (NCT03700320) was efficacious to reduce monthly migraine days, was associated with improvements in function and health-related quality of life, and rates of response increased throughout the course of the trial; further, the treatment was generally well tolerated with no new safety concerns identified [54][55][56]. A number of other studies are ongoing to evaluate the long-term safety and tolerability of atogepant in adult patients with episodic (NCT03939312) and episodic or chronic (NCT04686136 and NCT04437433) migraine.…”

New Generation Gepants: Migraine Acute and Preventive Medications

“…Long-term use of atogepant 60 mg for one year was tolerated, with 18% of adverse events considered to be related to the drug, namely upper respiratory tract infection, constipation, nausea, and urinary tract infection. None of the serious adverse events were considered related to the drug [ 61 ]. When administered in a single oral dose of 60 mg, atogepant was well tolerated in patients with hepatic impairment, with similar plasma levels, but increased systemic exposures to atogepant did not have a clinical translation [ 56 ].…”

Atogepant for the prevention of episodic migraine in adults

“… 32 The investigators reported no serious adverse events related to atogepant. 32 Cases of ALT or AST greater than three times ULN were reported in 2.4% (13/531) of participants in the atogepant group and 3.2% (6/109) in the standard of care group. 32 No cases of Hy’s Law were reported.…”

“… 32 Discontinuation due to adverse events occurred in 5.7% in the atogepant group. 32 The investigators reported no serious adverse events related to atogepant. 32 Cases of ALT or AST greater than three times ULN were reported in 2.4% (13/531) of participants in the atogepant group and 3.2% (6/109) in the standard of care group.…”