Gefurulimab Treatment Associated with Improved Daily Function and Muscle Strength in Generalized Myasthenia Gravis
KEY TAKEAWAYS
- Treatment with gefurulimab was associated with significant improvements in daily function and muscle strength vs placebo in adults with anti–acetylcholine receptor antibody–positive (AChR+) generalized myasthenia gravis (gMG), meeting all primary and secondary endpoints in the phase 3 PREVAIL trial.
- Benefits emerged as early as week 1 on the MG-ADL scale and were sustained through 26 weeks, while QMG improvements were observed by week 4.
- The once-weekly, self-administered subcutaneous C5 inhibitor showed a similar overall adverse-event rate to placebo; injection-site reactions were more frequent with gefurulimab, and no meningococcal infections occurred.
Once-weekly treatment with gefurulimab showed significant improvements in patient-reported measures of daily function and investigator-assessed muscle strength in adults with anti–acetylcholine receptor antibody–positive (AChR+) generalized myasthenia gravis (gMG), according to findings from the phase 3 PREVAIL trial (NCT05556096) published in JAMA Neurology. The investigational dual-binding nanobody met the study's primary and all secondary efficacy endpoints, with improvements beginning early after treatment initiation and continuing through week 26.
PREVAIL (NCT05556096) was a phase 3, double-blind, placebo-controlled trial conducted at 113 sites across 20 countries. Investigators randomized 260 adults with AChR+ gMG, Myasthenia Gravis Foundation of America class II to IV disease, and an Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 to gefurulimab (n=131) or placebo (n=129). Treatment was administered by once-weekly, weight-based subcutaneous self-injection for 26 weeks. Previously prescribed corticosteroids, nonsteroidal immunosuppressants, and intravenous or subcutaneous immunoglobulin were permitted at stable doses.
PREVAIL Trial Findings
- At week 26, least-squares mean MG-ADL scores decreased by 4.2 points with gefurulimab treatment vs 2.6 points with placebo, for a treatment difference of −1.6 (95% CI, −2.4 to −0.8; P<.001).
- QMG scores decreased by 4.5 vs 2.4 points, respectively, for a treatment difference of −2.1 (95% CI, −3.1 to −1.1; P<.001).
- A 5-point or greater Quantitative Myasthenia Gravis (QMG) improvement occurred in an adjusted 46.3% of gefurulimab-treated participants vs 25.2% with placebo (OR, 2.56; 95% CI, 1.42 to 4.62; P=.002).
- MG-ADL improvement was evident by week 1, while QMG and Myasthenia Gravis Composite improvements were observed at their first assessment at week 4 and sustained through week 26.
What the Findings Mean for Neurologic Practice
Gefurulimab targets complement component 5 (C5), an established therapeutic pathway in AChR-Ab+ gMG, but differs from existing C5-directed treatments in its administration schedule. Its dual-binding nanobody design supports once-weekly subcutaneous self-administration, potentially providing another administration option if the therapy receives regulatory approval.
Safety findings were generally comparable between groups. Treatment-emergent adverse events occurred in 75.6% of participants receiving gefurulimab and 80.6% receiving placebo, with most events mild to moderate. Injection-site reactions occurred more often with gefurulimab (9.9% vs 3.1%), although none resulted in treatment discontinuation. Serious adverse events occurred in 9.2% and 11.6% of participants, respectively, and no meningococcal infections were reported.
The 26-week randomized period does not establish long-term efficacy or safety, and the authors noted limited enrollment of Black or African American participants as another study limitation. The PREVAIL open-label extension is ongoing. Gefurulimab remains investigational; the study findings support continued evaluation of weekly subcutaneous C5 inhibition for AChR-Ab+ gMG.
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.