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Journal Article Ahead of print 5 citations

PubMed: 42507440 DOI: 10.1001/jamaneurol.2026.2333

Efficacy and Safety of Gefurulimab in Generalized Myasthenia Gravis: The PREVAIL Phase 3 Randomized Clinical Trial.

JAMA Neurol

Authors: Kelly G Gwathmey, Francesco Saccà, James F Howard, Tuan Vu, Jianying Xi, Mathias Mäurer, Tobias Ruck, Ha Young Shin, Masanori P Takahashi, Carlos Casasnovas, Marek Smilowski, Stojan Peric, Masayuki Masuda, Joachim Scholz, Shulian Shang, Min Yee, Sanjay Rakhade, Djillali Annane

Affiliations

  • Virginia Commonwealth University, Richmond.
  • University of Naples Federico II, Napoli, Italy.
  • University of North Carolina at Chapel Hill School of Medicine, Chapel Hill.
  • University of South Florida Morsani College of Medicine, Tampa.
  • Huashan Hospital, Fudan University, Shanghai, China.
  • Klinikum Würzburg Mitte, Würzburg, Germany.
  • Ruhr University Bochum, BG University Hospital Bergmannsheil, Bochum, Germany.
  • Yonsei University College of Medicine, Seoul, South Korea.
  • The University of Osaka Graduate School of Medicine, Osaka, Japan.
  • Bellvitge University Hospital-IDIBELL and CIBERER, Barcelona, Spain.
  • Silesian Neurology Medical Center, Katowice, Poland.
  • University of Belgrade-Faculty of Medicine, Belgrade, Serbia.
  • Tokyo Medical University, Tokyo, Japan.
  • Alexion, AstraZeneca Rare Disease, Boston, Massachusetts.
  • Reference Center for Neuromuscular Diseases of Northern, Eastern and Greater Paris (NEIDF), Raymond-Poincaré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris-Saclay University, UVSQ, Garches, France.

Abstract

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.

MeSH

Injections, Activities Of Daily Living, Safety, Therapeutics, Complement Activation, Nervous System Diseases, Myasthenia Gravis