Klygefa (gefurulimab) receives a positive CHMP opinion for AChR-positive generalised myasthenia gravis after positive Phase III PREVAIL results.
Written By: Creola Gonsalves, MS (Biotech)
Reviewed By: Pharmacally Editorial Team
Alexion, AstraZeneca Rare Disease today announced that Klygefa (gefurulimab) has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). The recommendation supports Klygefa’s use as an add-on to standard therapy for adult patients with anti-acetylcholine receptor (AChR) antibody-positive generalised myasthenia gravis (gMG).
The recommendation is based on results from the pivotal Phase III PREVAIL trial (ALXN1720-MG-301), which evaluated gefurulimab in adults with AChR-antibody-positive gMG.
Key findings from the study include:
- Primary Endpoint Achieved: At week 26, patients treated with Klygefa achieved a statistically significant improvement from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared to placebo, with a least-squares mean treatment difference of -1.6 points (95% CI, -2.4 to -0.8; p < 0.0001).
- Rapid & Sustained Response: Clinically meaningful improvements were observed as early as week one and maintained throughout the 26-week double-blind treatment period.
- Favorable Safety Profile: Gefurulimab was generally well tolerated, with safety outcomes consistent with prior clinical experience with C5 inhibitors, such as Soliris (eculizumab) and Ultomiris (ravulizumab), in gMG.
Targeting Terminal Complement Activation
gMG is a rare, chronic autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness. Approximately 85% of individuals living with gMG express antibodies against the acetylcholine receptor.
In AChR-positive disease, these autoantibodies trigger uncontrolled activation of the complement system at the neuromuscular junction. Complement-mediated destruction damages the junction and impairs signaling between nerves and muscles, leading to severe symptoms such as ocular weakness, speech and swallowing difficulties, loss of mobility, and potentially life-threatening respiratory compromise.
Gefurulimab is a novel dual-binding nanobody engineered to selectively inhibit complement component C5, preventing terminal complement activation. In addition to targeting C5, the nanobody binds serum albumin, extending its circulating half-life and enabling convenient, once-weekly subcutaneous self-administration.
Pivotal Trial Overview: PREVAIL
The global, randomized, double-blind, placebo-controlled Phase III PREVAIL study enrolled 260 adults across 20 countries in North America, Europe, Asia, and the Pacific region.
- Patient Population: Adults with confirmed gMG, positive AChR autoantibodies, and Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IV disease.
- Randomization & Dosing: Patients were randomized 1:1 to receive gefurulimab or placebo for 26 weeks. Treatment began with a single weight-based loading dose on Day 1, followed by weight-based maintenance dosing administered once weekly starting on Day 8.
“The PREVAIL trial demonstrated clear improvements in disease severity and daily functioning starting from the very first week of treatment through week 26, while offering the convenience of once-weekly self-administration,” said Tobias Ruck, MD, an investigator in the PREVAIL trial.
“This positive CHMP opinion builds on Alexion’s long-standing leadership in C5 complement inhibition with Soliris and Ultomiris, bringing us one step closer to delivering an innovative, flexible subcutaneous treatment option to gMG patients in Europe,” added Marc Dunoyer, Chief Executive Officer of Alexion.
Next Steps and Global Regulatory Status
Klygefa is already approved in Japan and select other countries for certain adult patients with gMG. Additional global regulatory filings based on the Phase III PREVAIL trial remain under active review in the United States, China, and other international markets.
Following this positive CHMP opinion, the next regulatory milestone in Europe will be a final decision by the European Commission regarding marketing authorization. If authorized, Klygefa will offer a first-in-class, once-weekly subcutaneous C5 inhibitor to adults living with AChR-antibody-positive gMG across the European Union.
Reference
Klygefa (gefurulimab) recommended for approval in the EU by CHMP for the treatment of adults with generalised myasthenia gravis (gMG), Astra Zeneca, 18 September 2026
Safety and Efficacy of ALXN1720 in Adults With Generalized Myasthenia Gravis, ClinicalTrials.gov ID NCT05556096
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.