Efficacy and Safety of Gefurulimab in Generalized Myasthenia Gravis

@article{gwathmey2026efficacy,
  title = {{Efficacy and Safety of Gefurulimab in Generalized Myasthenia Gravis}},
  author = {Kelly G. Gwathmey and Francesco Saccà and James F. Howard and Tuan Vu and Jianying Xi and Mathias Mäurer and Tobias Ruck and Ha Young Shin and Masanori P. Takahashi and Carlos Casasnovas and Marek Śmiłowski and Stojan Peric and Masayuki Masuda and Joachim Scholz and Shulian Shang and Min Yee and Sanjay Rakhade and Djillali Annane and Prevail Trial Investigators and Wolfgang Löscher and Carolina Mainella and Raffi Topakian and Wilson Marques and Maria de Penha Morita and Edmar Zanoteli and Marcela Costa and Roberto Rey and Alexandre Guerreiro and Alexandre Longo and Raffaele Iorio and Carolina Barnett-Tapia and Vera Bril and Zaeem Siddiqi and Annie Dionne and Matteo Garibaldi and Marcelo Rugiero and Hui Deng and Hongyu Zhou and Ruisheng Duan and Nicolai Rasmus Preisler and Qun Xue and Huan Yang and Zhangyu Zhou and Ting Chang and Bitao Bu and Qing Ke and Akira Tsujino and Akiyuki Uzawa and Hua Zhang and Chuanzhu Yan and Jin Wang and Feng Gao and Céline Tard and Florencia Aguirre and Shahram Attarian and Michelangelo Maestri and Saskia Bresch and Valentina Damato and Shahar Shelly and Aleksandra Nadaj-Pakleza},
  journal = {JAMA neurology},
  year = {2026},
  month = nov,
  doi = {10.1001/jamaneurol.2026.2333},
  url = {https://hal.science/hal-05850310v1},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Efficacy and Safety of Gefurulimab in Generalized Myasthenia Gravis
AU  - Kelly G. Gwathmey
AU  - Francesco Saccà
AU  - James F. Howard
AU  - Tuan Vu
AU  - Jianying Xi
AU  - Mathias Mäurer
AU  - Tobias Ruck
AU  - Ha Young Shin
AU  - Masanori P. Takahashi
AU  - Carlos Casasnovas
AU  - Marek Śmiłowski
AU  - Stojan Peric
AU  - Masayuki Masuda
AU  - Joachim Scholz
AU  - Shulian Shang
AU  - Min Yee
AU  - Sanjay Rakhade
AU  - Djillali Annane
AU  - Prevail Trial Investigators
AU  - Wolfgang Löscher
AU  - Carolina Mainella
AU  - Raffi Topakian
AU  - Wilson Marques
AU  - Maria de Penha Morita
AU  - Edmar Zanoteli
AU  - Marcela Costa
AU  - Roberto Rey
AU  - Alexandre Guerreiro
AU  - Alexandre Longo
AU  - Raffaele Iorio
AU  - Carolina Barnett-Tapia
AU  - Vera Bril
AU  - Zaeem Siddiqi
AU  - Annie Dionne
AU  - Matteo Garibaldi
AU  - Marcelo Rugiero
AU  - Hui Deng
AU  - Hongyu Zhou
AU  - Ruisheng Duan
AU  - Nicolai Rasmus Preisler
AU  - Qun Xue
AU  - Huan Yang
AU  - Zhangyu Zhou
AU  - Ting Chang
AU  - Bitao Bu
AU  - Qing Ke
AU  - Akira Tsujino
AU  - Akiyuki Uzawa
AU  - Hua Zhang
AU  - Chuanzhu Yan
AU  - Jin Wang
AU  - Feng Gao
AU  - Céline Tard
AU  - Florencia Aguirre
AU  - Shahram Attarian
AU  - Michelangelo Maestri
AU  - Saskia Bresch
AU  - Valentina Damato
AU  - Shahar Shelly
AU  - Aleksandra Nadaj-Pakleza
PY  - 2026
DA  - 2026/11/03
JO  - JAMA neurology
DO  - 10.1001/jamaneurol.2026.2333
UR  - https://hal.science/hal-05850310v1
AB  - Importance: Gefurulimab is a novel dual-binding nanobody that blocks complement component 5 activation. Complement activation is a key pathogenic mechanism in anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Objective: To evaluate the efficacy and safety of gefurulimab in adults with AChR-Ab+ gMG. Design, Setting, and Participants: This randomized clinical trial, PREVAIL, was a phase 3, double-blind, placebo-controlled study conducted at 113 sites in 20 countries. Patients were screened and randomized from November 2022 to November 2024; the randomized controlled treatment period was 26 weeks. Participants were adults (aged ≥18 years) with AChR-Ab+ gMG, a Myasthenia Gravis Foundation of America classification II through IV, and a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 5 or higher. Intervention: Gefurulimab or placebo via once-weekly subcutaneous self-injection. Main Outcomes and Measures: The primary end point was change from baseline in MG-ADL total score at week 26. The key secondary end point was change from baseline in Quantitative Myasthenia Gravis (QMG) total score at week 26. Safety was also assessed. Results: Of 405 patients screened, 145 were excluded; 260 met eligibility criteria and were randomized (gefurulimab, n = 131; placebo, n = 129); 249 patients completed the 26-week randomized controlled treatment period. The mean (SD) age was 52.8 (15.73) years; 157 (60.4%) patients were female and 103 (39.6%) were male. All primary and secondary end points were met with statistical significance. Improvements occurred within 1 week for MG-ADL score and 4 weeks for QMG score and were sustained through week 26. Least-squares mean change from baseline at week 26 for MG-ADL and QMG total scores for gefurulimab vs placebo were -4.2 vs -2.6 (treatment difference, -1.6; 95% CI, -2.4 to -0.8; P < .001) and -4.5 vs -2.4 (treatment difference, -2.1; 95% CI, -3.1 to -1.1; P < .001), respectively. The incidence of adverse events (AEs) was similar between groups. Most common treatment-emergent AEs with gefurulimab were injection site reactions, headache, back pain, and nasopharyngitis. No meningococcal infections were reported. Conclusions and Relevance: Gefurulimab demonstrated both early and sustained clinical benefit in AChR-Ab+ gMG and was well tolerated, supporting its potential as a convenient, once-weekly, self-administered treatment regimen. Trial Registration: ClinicalTrials.gov Identifier: NCT05556096.
SN  - 2168-6149
SN  - 2168-6157
ER  -