Efficacy and Safety of Subcutaneous Self-administered Gefurulimab in Generalized Myasthenia Gravis: Primary Results From the Phase Three, Randomized, Double-blind, Placebo-controlled PREVAIL Study
Kelly Gwathmey1, Francesco Sacca2, James Howard3, Tuan Vu4, Jianying Xi5, Mathias Maurer6, Tobias Ruck7, Ha Young Shin8, Masanori Takahashi9, Carlos Casasnovas10, Marek Śmiłowski11, Stojan Peric12, Masayuki Masuda13, Joachim Scholz14, Shulian Shang14, Min Yee14, Sanjay Rakhade14, Djillali Annane15
1Virginia Commonwealth University, 2University of Naples Federico II, 3University of North Carolina at Chapel Hill School of Medicine, 4University of South Florida Morsani College of Medicine, 5Huashan Hospital, Fudan University, 6Würzburg-Mitte Hospital, 7Department of Neurology, Ruhr University Bochum, BG University Hospital Bergmannsheil, 8Yonsei University College of Medicine, 9The University of Osaka Graduate School of Medicine, 10Bellvitge University Hospital, 11Medical University of Silesia, 12Clinical Center of Serbia, University of Belgrade, 13Tokyo Medical University, 14Alexion AstraZeneca Rare Disease, 15Hôpital Raymond Poincaré
Objective:
Evaluate the efficacy and safety of gefurulimab in adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG).
Background:
Gefurulimab, a novel, dual-binding nanobody, blocks complement component 5 activation. The phase 3, global, randomized, double-blind, placebo-controlled PREVAIL Study examines the efficacy and safety of gefurulimab in adults with AChR-Ab+ gMG (NCT05556096).
Design/Methods:
Adults with AChR-Ab+ gMG were randomized 1:1 to weekly subcutaneous self-administration of gefurulimab or placebo. The primary endpoint was change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score at week 26. Secondary endpoints included change from baseline in total scores of Quantitative Myasthenia Gravis (QMG) at weeks 4 and 26, and Myasthenia Gravis Composite (MGC) at week 26. Safety was also assessed.
Results:
260 patients (female, 60.4%; mean [SD] age at first dose, 52.8 [15.7] years; mean [SD] baseline MG-ADL total score, 9.0 [2.2]) were randomized (gefurulimab, n=131; placebo, n=129). Demographics and baseline disease characteristics were balanced between groups. All primary and secondary endpoints met statistical significance and demonstrated clinically meaningful improvements. Improvements in MG-ADL, QMG, and MGC total scores were observed at the first assessment after treatment initiation (MG-ADL, week 1; QMG and MGC, week 4) and sustained through week 26. Change from baseline at week 26 least squares mean (SEM) in MG-ADL was -4.2 (0.29) for gefurulimab and -2.6 (0.27) for placebo (treatment difference, ‑1.6 [0.40], P<0.0001), in QMG total score was -4.5 (0.37) for gefurulimab and -2.4 (0.34) for placebo (treatment difference, -2.1 [0.50]; P<0.0001), and in MGC total score was -7.8 (0.49) for gefurulimab and -4.7 (0.48) for placebo (treatment difference, -3.1 [0.69]; P<0.0001). No notable differences in adverse events were observed between the 2 groups; no meningococcal infections were reported.
Conclusions:
In PREVAIL, self-administered, once-weekly gefurulimab demonstrated rapid and sustained clinical benefit, supporting a convenient treatment regimen for patients with AChR-Ab+ gMG.
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