CHICAGO — Gefurulimab, an investigational C5 inhibitor, delivered rapid and sustained clinical benefit in patients with generalized myasthenia gravis (gMG) compared to a placebo, new data show.

The PREVAIL trial — one of the largest phase 3 trials in gMG — met all primary and secondary endpoints, with clinically meaningful improvements reported just 1 week after treatment and sustained at week 26 in patients with anti-acetylcholine receptor antibody-positive (AChR-Ab+) gMG.

C5 inhibitors have become an established treatment option for gMG, but most require intravenous administration.

With the advantage of self-administered subcutaneous (SC) weekly dosing, gefurulimab “has the potential to be the first therapeutic nanobody to offer patients with [AChR-Ab+] gMG an effective and convenient treatment option,” said principal investigator Kelly Gwathmey, MD, neurologist with Virginia Commonwealth University in Richmond, Virginia.

The findings were reported on April 21 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

Novel Agent With Sustained Clinical Benefit

Gefurulimab is a novel dual-binding nanobody that blocks C5 activation and binds to albumin. Its low molecular weight and extended half-life due to albumin binding enable SC dosing at weekly intervals.

The phase 3 PREVAIL study enrolled 260 adults with AChR-Ab+ gMG (Myasthenia Gravis Foundation of America class II to IV) and mean baseline Myasthenia Gravis Activities of Daily Living (MG-ADL) scores of 9.0.

Participants were randomly assigned (1:1) to receive weekly self-administered gefurulimab or placebo for 26 weeks, followed by an open-label extension.

The trial met its primary endpoint, with a greater reduction in the MG-ADL total score at week 26 with gefurulimab than with placebo (-4.2 vs -2.6) — a statistically significant treatment difference of -1.6 points (P < .0001), Gwathmey reported.

A clinically meaningful improvement in the MG-ADL score was observed as early as the first week after baseline, with benefits sustained throughout the 26-week treatment period, she noted.

Quantitative Myasthenia Gravis (QMG) total scores — a key secondary endpoint — improved by -4.5 points with gefurulimab vs -2.4 points with placebo at week 26 — a significant and clinically meaningful difference of -2.1 points (P < .0001), Gwathmey said.

Responder analyses further highlighted the treatment effect.

At week 26, about 66% of patients receiving gefurulimab achieved at least a 3-point improvement in the MG-ADL score compared with 52% of patients on placebo (P = .037) and 46% achieved a 5-point or greater improvement in the QMG score vs 25% on placebo (P = .0018).

These thresholds exceed established minimal clinically important differences, indicating meaningful functional gains, Gwathmey said.

‘Fantastic’ Addition to Treatment Toolkit

Gefurulimab was well tolerated, and the safety profile was consistent with previous trials of C5 inhibitors eculizumab and ravulizumab in gMG.

The percentage of participants with treatment-emergent adverse events (TEAEs) was similar between groups, and most were mild-to-moderate in severity (grade 1 or 2).

The most common TEAEs with gefurulimab were injection site reactions (10%), headache (10%), back pain (8%), and nasopharyngitis (7%). In the placebo group, the most common TEAEs were headache (12%), diarrhea (9%), and upper respiratory tract infection (8%). No meningococcal infections were reported.

“The prospect of this new therapy offers a fantastic addition to our toolkit for treating more refractory myasthenia gravis patients,” said Shanna Patterson, MD, neuromuscular specialist and professor of neurology at the Icahn School of Medicine at Mount Sinai in New York City, who commented on the findings for Medscape Medical News.

“Going forward, it will be interesting to see if efficacy comparison studies of some of the treatments in this class will emerge,” noted Patterson, who wasn’t part of the study.

Alexion, AstraZeneca Rare Disease, funded the study. Disclosure information for study authors is available in the original study publication. Patterson had no relevant disclosures.