Objective:

Provide an overview of PREVAIL, which is evaluating the efficacy and safety of gefurulimab in adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG).

Background:

Complement component 5 (C5) inhibitors are effective treatments for AChR-Ab+ gMG. Gefurulimab is a new investigational complement inhibitor that binds C5, blocks its enzymatic cleavage, and thus, inhibits the terminal complement pathway. Gefurulimab is suitable for subcutaneous (SC) self-administration. Its extended half-life allows for once-weekly injection. Gefurulimab is currently under investigation for treatment of AChR-Ab+ gMG in a phase 3, multicenter, randomized, double-blind, placebo-controlled study (PREVAIL; NCT05556096).

Design/Methods:

PREVAIL will enroll up to 254 adults with AChR-Ab+ gMG, including those with mild disease. Patients may continue taking previously prescribed therapies, including immunoglobulins. Patients are randomized 1:1 to weekly SC self-injection of gefurulimab or placebo. The primary endpoint is change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score at week 26. Secondary endpoints include change from baseline in Quantitative Myasthenia Gravis (QMG) total score and Myasthenia Gravis Composite (MGC) total score. Safety, pharmacokinetics, pharmacodynamics, immunogenicity, and quality of life will also be assessed. PREVAIL includes an open-label extension.

Results:

PREVAIL is recruiting patients at ~ 160 sites in North America, South America, Europe, Asia, and the Pacific region.

Conclusions:

This study examines the potential of the C5 inhibitor gefurulimab as a new treatment for patients with AChR-Ab+ gMG that can conveniently be self-administered at home through once-weekly SC injection. Results from PREVAIL will inform the clinical development program of gefurulimab.