Gefurulimab Maintains Myasthenia Gravis Benefits Through 1 Year

Investigational gefurulimab, a dual-binding nanobody that blocks complement component 5 (C5) activation, sustained functional improvements for 1 year in people with generalized myasthenia gravis, data from the open-label extension of the PREVAIL trial showed.

Improvements in scores on the Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Composite (MGC) scales continued through 52 weeks, reported Tuan Vu, MD, of the University of South Florida in Tampa, at the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) meeting in Orlando.

From baseline, MG-ADL scores (range 0-24) improved at 1 year by 5.3 points, Vu said. QMG scores (range 0-39) also improved by 5.3 points, and MGC scores (range 0-50) were 9.4 points better.

In patients who switched to gefurulimab from placebo at week 26, improvements emerged at the first assessments after starting treatment and were sustained through week 52, Vu added. In this group, MG-ADL scores improved by 4.9 points, QMG scores improved by 4.6 points, and MGC scores improved by 8.3 points.

The median treatment duration for patients receiving gefurulimab was 575 days. Over this period, treatment was well tolerated, with a safety profile consistent with the randomized controlled period of the study and no emerging safety signals, Vu said.

The phase III PREVAIL trial randomized 260 adults with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis to receive weekly self-administered subcutaneous gefurulimab or placebo for 26 weeks.

About 60% of participants in PREVAIL were female, and the mean age at the first dose of gefurulimab or placebo was 53 years. Mean baseline MG-ADL score was 9.0. The primary endpoint was the change from baseline in MG-ADL score at 26 weeks. Change in QMG score was a key secondary endpoint.

The trial met all primary and secondary endpoints. Improvements occurred within 1 week for MG-ADL scores and 4 weeks for QMG scores and were sustained through week 26.

The incidence of adverse events was similar between groups, with injection site reactions, headache, back pain, and nasopharyngitis the most common treatment-emergent adverse events with gefurulimab. No meningococcal infections were reported.

Complement C5 inhibitors can effectively treat anti-AChR antibody-positive generalized myasthenia gravis. Three C5 inhibitors are approved by the FDA for myasthenia gravis: eculizumab (Soliris), ravulizumab (Ultomiris), and zilucoplan (Zilbrysq). The drugs carry a boxed warning about the increased risk of Neisseria meningitidis, and patients are required to comply with recommendations for meningococcal vaccinations.

Gefurulimab binds to serum albumin to provide an extended half-life, allowing once-weekly dosing. “The safety profile was in line with earlier studies of C5 inhibitors in generalized myasthenia gravis,” observed Christiane Schneider-Gold, MD, and Ralf Gold, MD, both of Ruhr University Bochum in Germany. “In addition, no unexpected safety concerns were identified in patients recruited across 20 countries,” they wrote in a JAMA Neurology editorial this year.

“Despite rather well-tolerated subcutaneous application, it remains an interesting matter which position gefurulimab will eventually gain in the continuously evolving treatment landscape in generalized myasthenia gravis and among the group of complement inhibitors,” Schneider-Gold and Gold noted.

Of 249 patients who completed the randomized controlled period in PREVAIL, all entered the open-label extension. At the data cutoff point in November 2025, 211 had continued treatment. The demographics and baseline characteristics of patients in the open-label extension were similar across treatment groups, Vu said.

In September, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended gefurulimab for EU approval. The drug is also under FDA review.