SAN FRANCISCO — Gefurulimab, a self-administered, subcutaneous C5 inhibitor therapy for generalized myasthenia gravis (gMG) was linked to clinically meaningful improvements in patient function as early as 1 week after initiation and met its primary endpoint in the phase 3 PREVAIL trial.

In the 26-week, randomized, double-blind, placebo-controlled trial of adult patients with gMG assigned to receive gefurulimab (n = 131) or placebo (n = 129), the least squares mean change from baseline Myasthenia Gravis Activities of Daily Living (MG-ADL) total score was -4.2 points for the drug vs -2.6 points for placebo, for a treatment difference of -1.6 points (P < .0001). 

“Gefurulimab may offer patients with anti-acetylcholine receptor [AChR] antibody-positive generalized myasthenia gravis a convenient and effective treatment option,” said study investigator Kelly G. Gwathmey, MD, a neurologist at VCU Health, Richmond, Virginia.

She noted that C5 inhibitors are already well established as effective and well tolerated treatments for AChR-antibody-positive gMG. 

The findings were presented on October 29 at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2025.

Sustained Benefit

Gefurulimab is a new dual-binding nanobody designed to block C5 activation while also attaching to albumin. Its small molecular size — about 28 kDa, compared with roughly 150 kDa for a standard monoclonal antibody — combined with its albumin binding gives it an extended half-life that supports weekly subcutaneous dosing. The drug can be administered via prefilled syringe or autoinjector.

Researchers presented the topline results from the phase 3 PREVAIL study, which was conducted to evaluate the efficacy and safety of gefurulimab in gMG. 

Study participants had AChR antibody-positive gMG at Myasthenia Gravis Foundation of America levels II-IV and MG-ADL scores of at least 5. There was no requirement for previous treatment failure, although patients had to be on stable standard-of-care therapy.

In the gefurulimab group, participants were an average of 53.0 years of age; 59.5% were female; and 52.7% were White, 32.8% Asian, 2.3% Black/African American, 1.5% multiple races, and 10.7% other, unknown, or race not reported. In the placebo group, the average age was 52.7 years; 61.2% of participants were female; and 57.4% were White, 29.5% Asian, 2.3% Black/African American, 10.9% other, unknown, or race not reported. 

At baseline, both groups had identical mean MG-ADL total scores of 9.0. The mean Quantitative Myasthenia Gravis (QMG) total scores were also comparable: 14.9 in the gefurulimab group and 14.7 in the placebo group. Four participants in the gefurulimab group discontinued treatment, compared with seven in the placebo group.

At 26 weeks, the least squares mean change from baseline QMG total score was -4.5 points for gefurulimab vs -2.4 points for placebo (treatment difference, -2.1 points; 95% CI, -3.1 to -1.1; P < .0001).

Gwathmey noted that the timing of benefit was particularly noteworthy. “Meaningful improvements were observed early as the first post-baseline MG-ADL total score assessment at week 1, and QMG total score assessment at week 4, and these improvements were sustained for the duration of the 26 weeks,” she said.

Gefurulimab was well tolerated, with a safety profile comparable to that of other terminal complement inhibitors, including eculizumab and ravulizumab. “There were no new safety concerns identified, and no meningococcal infections were observed,” said Gwathmey.

Adverse events were reported in 75.6% of participants in the gefurulimab group. The most common were injection-site reactions, headache (9.9%), and back pain (7.6%). Adverse events also occurred in 80.6% of those in the placebo group, most frequently headache (12.4%), diarrhea (8.5%), and upper respiratory infection (7.8%).

One treatment-emergent adverse event led to treatment discontinuation in each group; the event in the gefurulimab group was deemed serious. In total, serious adverse events presented in 9.2% of the gefurulimab group, and 11.6% of the placebo group. There was one unrelated death in each group.

Long-Term Data Will Tell the Tale

Yuebing Li, MD, PhD, a neurologist at Cleveland Clinic in Ohio who was not involved with the research, praised the study’s quality in an interview with Medscape Medical News. 

“However,” Li said, “the MG-ADL improvement between drug and control groups is modest, albeit statistically significant and clinically meaningful.”

Li noted that this monoclonal antibody-nanobody hybrid is considerably smaller than other commercially available monoclonal antibodies and was designed with the expectation that its compact size would allow better tissue penetration and more direct complement inhibition at the neuromuscular junction, potentially leading to greater efficacy.

“We will have to be patient and await results on its long-term efficacy, but results from this short-term study suggest that its efficacy is comparable to other complement inhibitors.”

Li noted that the drug appears to be safe in the short term, with no surprising safety findings. “However, the long-term complications of infections are not easily reflected in a trial that lasts 6 months.”

Alexion and AstraZeneca Rare Disease funded the study. Gwathmey disclosed relationships with AcademicCME, Alexion, AstraZeneca Rare Disease, Amgen, Argenx, and UCB. Other study author disclosures were not provided. Li disclosed relationships with Alexion, Argenx, Amgen, Johnson & Johnson, and Vertex.