CHMP Backs AstraZeneca's Klygefa (gefurulimab) for Generalised Myasthenia Gravis in the EU
核心洞察
The EMA's CHMP has recommended approval of Alexion's Klygefa (搜索) (gefurulimab) as an add-on therapy for anti-AChR antibody-positive adults with generalised myasthenia gravis (搜索).
The positive opinion rests on the pivotal PREVAIL Phase III trial, where gefurulimab improved MG-ADL total score at week 26 versus placebo by -1.6 (95% CI: -2.4, -0.8; p<0.0001).
If approved, Klygefa (搜索) would be the first and only dual-binding nanobody C5 inhibitor for this population, given once weekly by subcutaneous self-administration via autoinjector.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (搜索) has recommended approval of Klygefa (搜索) (gefurulimab) as an add-on to standard therapy for adults with generalised myasthenia gravis (搜索) (gMG) who are anti-acetylcholine receptor (搜索) (AChR) antibody-positive. Alexion, AstraZeneca Rare Disease, announced the positive opinion on 18 September 2026; the CHMP adopted it 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.
If approved, Klygefa (搜索) would be the first and only dual-binding nanobody C5 inhibitor for this patient population, the company said. The recommendation is based on results from the pivotal PREVAIL Phase III trial, which were 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.
PREVAIL Results
In PREVAIL, Klygefa (搜索) met its primary endpoint, demonstrating 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; p<0.0001). A clinically meaningful improvement was observed as early as week one and was sustained through week 26. 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.
Klygefa (搜索) was generally well tolerated, and the safety profile was consistent with previous trials of the C5 inhibitors eculizumab and ravulizumab in gMG. According to the EMA opinion summary, the most common side effects with Klygefa are injection site reactions, back pain, arthralgia, muscle spasms, myalgia, nausea and vomiting. 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.
Trial Design and Dosing
PREVAIL (ALXN1720-MG-301) is a global, Phase III, randomised, double-blind, placebo-controlled, parallel, multicentre study evaluating the safety and efficacy of Klygefa (搜索) in adults with gMG. The trial enrolled 260 patients from 20 countries across North America, Europe, Asia and the Pacific region. Participants were required to have a confirmed myasthenia gravis diagnosis at least three months prior to the screening visit, a positive serological test for autoantibodies against AChR, and Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening.
Patients were randomised 1:1 to receive Klygefa (搜索) or placebo for a total of 26 weeks in the randomised controlled treatment period. They received a single weight-based loading dose on Day 1, followed by regular weight-based maintenance dosing beginning on Day 8 and once every week thereafter. The primary endpoint was the change from baseline in the MG-ADL total score, a patient-reported scale that assesses patients' abilities to perform daily activities, assessed at week 26 along with multiple secondary endpoints evaluating improvement in disease-related measures. Patients who completed the randomised controlled treatment period were eligible to continue into an open-label extension period evaluating the safety and efficacy of Klygefa, which is ongoing.
Mechanism and Product Profile
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 (搜索) as a novel dual-binding nanobody optimised for subcutaneous self-administration, given once weekly via autoinjector.
Klygefa (搜索) 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 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. Gefurulimab has been granted Orphan Drug Designation in the US for the treatment of myasthenia gravis.
Klygefa (搜索) 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.
Investigator and Company Comment
Tobias Ruck, MD, Director of the Department of Neurology at BG University Hospital Bergmannsheil Bochum, Ruhr-University Bochum, and an investigator in the trial, said: "For people living with gMG, unpredictable symptoms can quickly become incapacitating or life-threatening. In the PREVAIL Phase III trial, 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. With this positive CHMP opinion patients may soon have the option of a novel treatment option that could help them spend less time thinking about their care and more time living their lives."
Marc Dunoyer, Chief Executive Officer of Alexion, said: "This positive CHMP opinion is an important step towards bringing Klygefa (搜索), an innovative dual-binding nanobody C5 inhibitor, to people living with gMG in the EU. Building on our pioneering work demonstrating the efficacy of C5 inhibition with Soliris and Ultomiris, Klygefa is designed to offer rapid and sustained symptom control with convenient once-weekly subcutaneous self-administration via autoinjector."
Disease Burden
gMG is a rare autoimmune disorder characterised by reduced muscle function and severe muscle weakness. Eighty-five percent of people with gMG are AChR antibody-positive, meaning they produce specific antibodies that bind to signal receptors at the neuromuscular junction, the connection point between nerve cells and the muscles they control. This binding activates the complement system, causing the immune system to attack the neuromuscular junction, leading to inflammation and a breakdown in communication between the brain and the muscles.
gMG can occur at any age, but it most commonly begins for women before the age of 40 and for men after the age of 60. Initial symptoms may include slurred speech, double vision, droopy eyelids and lack of balance; these can often lead to more severe symptoms as the disease progresses, such as 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.
Klygefa (搜索) is approved in Japan and other countries for certain adults with gMG. Regulatory submissions based on the PREVAIL results are under review in the US, China and additional countries.