Phase 3 Trial Shows Gefurulimab Improves Generalized Myasthenia Gravis
USA: A phase 3 randomized controlled trial demonstrated that once-weekly, self-administered gefurulimab significantly improved daily functioning and muscle strength in adults with generalized myasthenia gravis compared with placebo by week 26. The treatment provided rapid and sustained clinical benefits, while most adverse events were mild and occurred at similar rates in both the gefurulimab and placebo groups.
The findings come from the PREVAIL phase 3 randomized clinical trial, published in JAMA Neurology. The study was led by Kelly G. Gwathmey of Virginia Commonwealth University in Richmond and colleagues. Researchers evaluated the efficacy and safety of gefurulimab, a novel dual-binding nanobody that blocks complement component 5 (C5), a key driver of disease in anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG).
PREVAIL was a multicenter, double-blind, placebo-controlled trial conducted across 113 sites in 20 countries. Adults aged 18 years or older with AChR-Ab+ generalized myasthenia gravis, 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 were enrolled. Participants were randomly assigned to receive either gefurulimab or placebo through once-weekly subcutaneous self-injections for 26 weeks.
A total of 405 patients were screened, and 260 met eligibility criteria and underwent randomization, with 131 receiving gefurulimab and 129 receiving placebo. Overall, 249 participants completed the treatment period. The average age of participants was 52.8 years, and approximately 60% were women.
Key findings from the study include:
- Gefurulimab met both the primary and key secondary efficacy endpoints with statistically significant improvements over placebo.
- MG-ADL scores improved within 1 week of starting treatment and remained improved through week 26.
- Muscle strength, assessed using the Quantitative Myasthenia Gravis (QMG) score, improved within 4 weeks and was sustained throughout the study.
- At week 26, patients receiving gefurulimab showed greater reductions in MG-ADL scores (−4.2 vs −2.6) and QMG scores (−4.5 vs −2.4) than those receiving placebo.
- The overall incidence of adverse events was similar between the gefurulimab and placebo groups.
- The most frequently reported treatment-emergent adverse events with gefurulimab were injection-site reactions, headache, back pain, and nasopharyngitis.
- No cases of meningococcal infection were reported during the trial.
The researchers noted that the six-month follow-up limits assessment of long-term efficacy and safety. They also acknowledged that continued background myasthenia gravis medications and the underrepresentation of Black or African American patients may have affected the findings' generalizability.
Overall, the PREVAIL trial suggests that once-weekly, self-administered gefurulimab provides rapid, sustained clinical benefit and is well tolerated in adults with AChR-Ab+ generalized myasthenia gravis. Ongoing extension studies will further assess its long-term safety and efficacy.
Reference:
Gwathmey KG, Saccà F, Howard JF, 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
Next Story