Phase 3 PREVAIL Trial: Gefurulimab Improves Outcomes in Generalized Myasthenia Gravis
KEY TAKEAWAYS
- Once-weekly gefurulimab produced improvements in daily function within 1 week and muscle strength by the first QMG assessment at week 4, with benefits sustained through week 26.
- More participants receiving gefurulimab achieved prespecified clinically relevant response thresholds on MG-ADL and QMG measures than those receiving placebo.
- Adverse event rates were comparable between groups, with no meningococcal infections reported during the 26-week randomized period.
Gefurulimab, an investigational dual-binding nanobody targeting complement component 5 (C5), improved activities of daily living and muscle strength compared with placebo in adults with anti–acetylcholine receptor antibody–positive (AChR-Ab+) generalized myasthenia gravis (gMG), according to results from the phase 3 PREVAIL trial published in JAMA Neurology.
PREVAIL (NCT05556096) was a double-blind, placebo-controlled trial conducted at 113 sites across 20 countries. Investigators randomized 260 adults with AChR-Ab+ gMG, Myasthenia Gravis Foundation of America class II to IV disease, and a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 to once-weekly subcutaneous gefurulimab (n=131) or placebo (n=129) for 26 weeks. The primary end point was change in MG-ADL score at week 26; change in Quantitative Myasthenia Gravis (QMG) score was the key secondary end point.
What the Trial Revealed
- MG-ADL scores improved by a least-squares mean of 4.2 points with gefurulimab vs 2.6 points with placebo (difference, –1.6; 95% CI, –2.4 to –0.8; P<.001).
- QMG scores improved by 4.5 vs 2.4 points, respectively (difference, –2.1; 95% CI, –3.1 to –1.1; P<.001).
- A ≥5-point QMG improvement occurred in an adjusted 46.3% vs 25.2% of participants (P=.002).
Treatment-emergent adverse events occurred in 75.6% of gefurulimab-treated participants and 80.6% receiving placebo. Injection-site reactions occurred in 9.9% and 3.1%, respectively. No meningococcal infections were reported. The authors noted that the 26-week randomized period was insufficient to assess long-term efficacy and safety; an open-label extension is ongoing.
Source:
Gwathmey KG, Saccà F, Howard JF Jr, et al. Efficacy and safety of gefurulimab in generalized myasthenia gravis: the PREVAIL phase 3 randomized clinical trial. JAMA Neurol. Published online July 27, 2026. doi:10.1001/jamaneurol.2026.2333.