Gefurulimab Recommended for EU Approval in Generalized Myasthenia Gravis

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended approval of gefurulimab (Klygefa; AstraZeneca/Alexion), a weekly, self-administered complement C5 inhibitor, for adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG) as an add-on to standard therapy.¹

The positive opinion was based on data from the phase 3 PREVAIL trial (NCT05556096), in which gefurulimab met its primary endpoint and all secondary endpoints, with a final decision from the European Commission expected in the coming months. Regulatory submissions for gefurulimab are also under review in the United States, China, and additional countries.

“For people living with gMG, unpredictable symptoms can quickly become incapacitating or life-threatening,” Tobias Ruck, MD, Director Department of Neurology, BG University Hospital Bergmannsheil Bochum, Ruhr-University Bochum and investigator in the trial, said in a statement accompanying the CHMP announcement.¹

Mechanistically, gefurulimab is a dual-binding nanobody that targets complement component 5 (C5) to block formation of the membrane attack complex implicated in neuromuscular junction damage, while a concurrent albumin-binding domain extends the drug's half-life to enable once-weekly dosing. It is administered as a weight-based loading dose on day 1, followed by weight-based maintenance doses beginning on day 8 and then weekly, delivered subcutaneously via a self-administered autoinjector.

PREVAIL (ALXN1720-MG-301) was a global, randomized, double-blind, placebo-controlled phase 3 trial that enrolled 260 adults with AChR-Ab+ gMG across 20 countries, randomly assigned 1:1 to weekly subcutaneous gefurulimab or placebo over a 26-week double-blind period with an optional open-label extension.^2,4

At week 26, gefurulimab produced a mean 4.2-point reduction in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score compared with a 2.6-point reduction with placebo, a treatment difference of -1.6 (95% CI, -2.4 to -0.8; P <.001), with improvement apparent as early as week 1. Quantitative Myasthenia Gravis (QMG) total scores also improved by 4.5 points with gefurulimab versus 2.4 points with placebo (difference, -2.1; 95% CI, -3.1 to -1.1; P <.001), and significantly more gefurulimab-treated patients achieved a clinically meaningful 5-point or greater QMG improvement (46.3% vs 25.2%; P =.002).²

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In PREVAIL, treatment-emergent adverse events (TEAEs) occurred in 75.6% of gefurulimab-treated patients compared with 80.6% of those receiving placebo. Injection-site reactions were more frequent with gefurulimab (9.9% vs 3.1%), and no meningococcal infections were reported during the 26-week randomized period, though complement inhibitors carry a labeled risk of meningococcal infection that typically requires vaccination and monitoring.²

“Results from the PREVAIL Phase III trial demonstrating early and lasting benefits in MG-ADL and QMG scores support potential for gefurulimab to offer efficacious, convenient self-administered treatment,” Kelly Gwathmey, MD, principal investigator and chief of the neuromuscular division at Virginia Commonwealth University, said at the time of the announced data.³

Gefurulimab's clinical development moved from an initial phase 1 study directly into the pivotal PREVAIL trial; a formal phase 2 study of the drug in myasthenia gravis does not appear to have been conducted. The phase 1 study, a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose trial in healthy volunteers, evaluated the safety, tolerability, pharmacokinetics, and immunogenicity of subcutaneous and intravenous gefurulimab and was presented at the 2023 American Academy of Neurology Annual Meeting.⁵

REFERENCES
1. Klygefa (gefurulimab) recommended for approval in the EU by CHMP for the treatment of adults with generalised myasthenia gravis (gMG). News release. AstraZeneca. Published September 18, 2026. Accessed September 21, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/klygefa-recommended-for-approval-in-the-eu.html
2. 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
3. Gefurulimab demonstrates statistically significant and clinically meaningful improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) at week 26 with clinically meaningful improvement seen as early as week one in adults with gMG in PREVAIL Phase III trial. News release. AstraZeneca. Published October 30, 2025. Accessed September 21, 2026. https://www.astrazeneca.com/media-centre/press-releases/2025/positive-results-from-prevail-phase-iii-trial-at-aanem-mgfa-scientific-session.html
4. A study to evaluate gefurulimab in adult participants with generalized myasthenia gravis (PREVAIL). ClinicalTrials.gov identifier: NCT05556096. Accessed September 21, 2026. https://clinicaltrials.gov/study/NCT05556096
5. Ortiz S, et al. Safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of subcutaneous and intravenous ALXN1720 in healthy volunteers: a phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study (P1-5.016). Neurology. 2023;100(17 suppl 2). doi:10.1212/WNL.0000000000203482