Injectable Nanobody Wins FDA Approval for Myasthenia Gravis

The FDA on Friday approved injectable gefurulimab (Klygefa), a dual-binding nanobody that blocks complement component 5 (C5) activation, to treat generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive.
The approval comes in the wake of the phase III PREVAIL trial, which randomized 260 adults with anti-AChR antibody-positive generalized myasthenia gravis to receive weekly self-administered subcutaneous gefurulimab or placebo for 26 weeks. The trial met the primary endpoint, showing an improvement in scores on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale versus placebo at week 28, with a treatment difference of -1.6 points.
MG-ADL scores range 0-24 points; improvements emerged in week 1 and continued through week 26. Quantitative Myasthenia Gravis scores — a key secondary endpoint — also improved by week 4 compared with placebo, and improvement was sustained throughout the study.
The drug is available only through a risk evaluation and mitigation strategy (REMS) program. The drug carries a boxed warning for serious and life-threatening infections caused by Neisseria meningitidis. Three other C5 inhibitors have been approved by the FDA for myasthenia gravis: eculizumab (Soliris), ravulizumab (Ultomiris), and zilucoplan (Zilbrysq). All carry a similar warning, and patients are required to comply with recommendations for meningococcal vaccinations.
In PREVAIL, the percentage of participants with treatment-emergent adverse events (TEAEs) was similar between the gefurulimab and placebo groups. Most TEAEs were mild to moderate (grade 1 or 2).
In the gefurulimab group, the most common TEAEs were injection site reactions (9.9%), headache (9.9%), and back pain (7.6%). Twelve people treated with gefurulimab had serious adverse events. One death occurred, which was not considered to be related to treatment.
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 a JAMA Neurology editorial earlier this year. “In addition, no unexpected safety concerns were identified in patients recruited across 20 countries,” they wrote.
“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.
Data from the open-label extension of PREVAIL recently showed that gefurulimab sustained functional benefits through 52 weeks.

In September, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended gefurulimab for EU approval.