CHMP Recommends AstraZeneca’s Klygefa for Generalised Myasthenia Gravis

AstraZeneca announced on 18 September 2026 (AZN ) that Klygefa (gefurulimab), developed by its rare disease unit Alexion, has been recommended for approval in the European Union as an add-on to standard therapy for adults with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted the positive opinion on 17 September 2026, according to the EMA’s medicine record for Klygefa, which names Alexion Europe SAS as the applicant and lists the application as pending a European Commission decision. The recommendation is based on the pivotal PREVAIL Phase III trial, in which AstraZeneca reported Klygefa met its primary endpoint of improved daily-living function at week 26.

In the PREVAIL results, Klygefa demonstrated improvement from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score at week 26 compared with placebo, with a treatment difference of -1.6 (95% CI: -2.4, -0.8) and p<0.0001, the company reported. A clinically meaningful improvement was observed as early as week one and was sustained through week 26. If approved, Klygefa will be the first and only dual-binding nanobody C5 inhibitor for this patient population, AstraZeneca said.

PREVAIL Phase III Design and Disclosure History

PREVAIL (ALXN1720-MG-301) is a global, randomised, double-blind, placebo-controlled, parallel, multicentre Phase III study that enrolled 260 patients from 20 countries across North America, Europe, Asia and the Pacific region. Participants needed a confirmed myasthenia gravis diagnosis at least three months before screening, a positive serological test for anti-AChR autoantibodies, and Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening. Patients were randomised 1:1 to Klygefa or placebo over a 26-week controlled treatment period, receiving a single weight-based loading dose on Day 1 followed by weight-based maintenance dosing once weekly from Day 8. The primary endpoint, change from baseline in MG-ADL total score, was assessed at week 26 along with multiple secondary endpoints, and patients who completed the controlled period were eligible to enter an open-label extension that remains ongoing.

AstraZeneca first disclosed top-line PREVAIL results on 24 July 2025, reporting that gefurulimab met the primary and all secondary endpoints with no new safety signals observed. The results were later presented at the Myasthenia Gravis Foundation of America Scientific Session during the American Association of Neuromuscular & Electrodiagnostic Medicine 2025 Annual Meeting and published in JAMA Neurology on 27 July 2026. Klygefa was generally well tolerated in the trial, with a safety profile consistent with previous studies of the C5 inhibitors eculizumab and ravulizumab in gMG, the company said.

EMA Product Profile and Meeting Outcome

Klygefa will be available as a 300 mg solution for injection in a pre-filled pen or a pre-filled syringe, according to the EMA opinion summary. The active substance gefurulimab is classified as an immunosuppressant under ATC code L04AJ12, and the medicine carries EMA product number EMEA/H/C/006558. The EMA states that the benefits of Klygefa are a reduction in disease severity and improvements in function, measured using the MG-ADL, Quantitative Myasthenia Gravis and Myasthenia Gravis Composite scores, together with quality-of-life improvements measured using the revised 15-item Myasthenia Gravis Quality of Life scale; these benefits were demonstrated with weight-based dosing in the 26-week randomised, placebo-controlled trial and its subsequent open-label phase. The most common side effects with Klygefa are injection site reactions, back pain, arthralgia, muscle spasms, myalgia, nausea and vomiting. The medicine is intended for use under the guidance of healthcare professionals experienced in the management of patients with neuromuscular disorders, and the summary of product characteristics will be published in all official EU languages after the European Commission grants the marketing authorisation.

Klygefa was one of 12 new medicines recommended for approval at the CHMP’s meeting of 14-17 September 2026, which also delivered positive opinions on 11 extensions of therapeutic indications, according to the committee’s published meeting highlights.

Gefurulimab binds to and blocks the C5 complement protein, preventing its cleavage into the pro-inflammatory anaphylatoxin C5a and C5b and thereby blocking pathogenic activation of the terminal complement pathway, the EMA record states. The molecule also binds to serum albumin, extending its half-life and allowing weekly dosing. AstraZeneca describes Klygefa as a novel dual-binding nanobody optimised for subcutaneous self-administration, given once weekly via autoinjector. Gefurulimab has been granted Orphan Drug Designation in the US for the treatment of myasthenia gravis.

gMG is a rare autoimmune disorder characterised by reduced muscle function and severe muscle weakness, according to the company’s announcement. Eighty-five percent of people with gMG are AChR antibody-positive, producing antibodies that bind to signal receptors at the neuromuscular junction; the binding activates the complement system, causing the immune system to attack the junction and leading to inflammation and a breakdown in communication between the brain and the muscles. The disease most commonly begins before age 40 in women and after age 60 in men, with initial symptoms that can include slurred speech, double vision, droopy eyelids and lack of balance, potentially progressing to impaired swallowing, choking, extreme fatigue and respiratory failure. AstraZeneca data on file estimate that 82,500 people are diagnosed with gMG across Germany, France, the UK, Italy and Spain, of whom 66,000 are AChR-positive.

Marc Dunoyer, Chief Executive Officer of Alexion, said: “This positive CHMP opinion is an important step towards bringing Klygefa, an innovative dual-binding nanobody C5 inhibitor, to people living with gMG in the EU.” He said Klygefa builds on the company’s work demonstrating the efficacy of C5 inhibition with Soliris and Ultomiris and is designed to offer rapid and sustained symptom control with once-weekly subcutaneous self-administration.

Tobias Ruck, Director of the Department of Neurology at BG University Hospital Bergmannsheil Bochum, Ruhr-University Bochum, and an investigator in the trial, said gefurulimab “demonstrated the ability to improve measures of disease severity and daily function with the convenience of once weekly subcutaneous self-administration, as early as one week and through the 26-week study period.”

Klygefa is approved in Japan and other countries for certain adults with gMG, and regulatory submissions based on the PREVAIL results are under review in the US, China and additional countries, AstraZeneca said.