An international phase III study has proven the safety and efficacy of gefurulimab, a once-weekly self-administered treatment for anti-acetylcholine receptor antibody-positive generalised myasthenia gravis.
A novel dual-binding nanobody could offer patients with generalised myasthenia gravis an effective and convenient treatment option, according to new research.
“Gefurulimab met all primary and secondary end points in this phase III trial, demonstrating its efficacy for the treatment of adults with [anti-acetylcholine receptor antibody-positive generalised myasthenia gravis],” the researchers behind the new study wrote in JAMA Neurology.
“Clinically meaningful improvements…were observed as early as the first assessment after treatment initiation…and [were] sustained through week 26, demonstrating an early onset of action and continued treatment effect.”
Two hundred and sixty adults (aged ≥18 years) with a documented diagnosis of gMG made at least 90 days before screening, a positive serological test for anti-AchR autoantibodies, a Myasthenia Gravis Foundation of America classification of II to IV, and a Myasthenia Gravis Activities of Daily Living total score of ≥5 were recruited from 113 sites across 20 countries as part of the PREVAIL trial. Patients who had been treated with a complement or FcRn inhibitor with less than five half-lives before the start of the trial were excluded. All participants had been vaccinated against Neisseria meningitidis before receiving their first dose of the trial intervention.
One hundred and thirty-one patients were randomised to receive gefurulimab (78 females, mean age of 53.0 years at the start of the trial) and 129 received placebo (79 females, mean age 52.7 years). Both groups had an average MG-ADL score of 9 at baseline.
Patients received an initial loading dose of gefurulimab (600mg or 900mg, depending on their body weight) or placebo at baseline (day 1) via subcutaneous injection before receiving maintenance doses of gefurulimab (300mg or 600mg) or placebo on day 8 and then every week until 26 weeks. A greater number of patients who received placebo discontinued their treatment prior to the 26-week mark compared to the number of patients who received gefurulimab (seven versus four).
The primary outcome (the change in MG-ADL total score from baseline to 26 weeks) favoured gefurulimab over placebo, with patients in the active treatment group displaying an average least-squares mean reduction of 4.2 points (95% confidence interval -4.7 to -3.6) and patients in the control group displaying an average reduction of 2.6 points (-3.1 to -2.0).
The secondary outcome measures also favoured the active intervention. Patients receiving gefurulimab had greater reductions in their Quantitative Myasthenia Gravis scores from baseline to week four (least-squares mean change -3.3 [-3.9 to -2.7] versus -1.5 [-2.0 to -1.0]) and baseline to week 26 (-4.5 [-5.2 to -3.8] versus -2.4 [-3.1 to -1.7]), as well as greater reductions in their Myasthenia Gravis Composite scores from baseline to week 26 (-7.8 [-8.8 to -6.8] versus -4.7 [-5.7 to -3.8]), than patients who received placebo.
Related
Gefurulimab treatment was also associated with being more likely to have a ≥5 point reduction in QMG score at week 26 (odds ratio 2.56 [1.42-4.62]) and a ≥3 point reduction in MG-ADL score (1.74 [1.03-2.93]) compared to placebo.
“These findings, along with clinical and real-world evidence from approved C5 inhibitors, reinforce the predominant role of complement activation in the pathogenesis of gMG and support C5 inhibition as an effective therapeutic approach for this disease,” said the researchers.
“While cross-trial comparisons should be interpreted with caution because of differences in trial design, the treatment effect of gefurulimab fell within the range of MG-ADL improvements reported in the phase 3 trials of advanced gMG therapies currently available. Gefurulimab also showed an early onset of efficacy consistent with other complement inhibitors.”
The researchers felt gefurulimab’s design offered several advantages over other available treatments, some of which are administered intravenously and/or more frequently than once per week.
“The nanobody-based platform supports the development of gefurulimab with a lower molecular weight than conventional antibodies, enabling subcutaneous self-administration,” they wrote.
“The bispecific design allows gefurulimab to bind to albumin and C5, thereby blocking C5 activation while leveraging albumin-mediated recycling to extend half-life and support the once-weekly dosing interval.
“Collectively, these design features render gefurulimab a convenient treatment option offering patients more autonomy and greater flexibility compared with currently available therapies. Additionally, the binding sites for gefurulimab and immunoglobulin G on the FcRn differ, allowing for concomitant treatment with immunoglobulin, which is an important consideration for the treatment of MG.”
Participants in both groups reported treatment-emergent adverse events at similar rates: 75.6% in the gefurulimab group and 80.6% in the placebo group. Headache (9.9%), back pain (7.6%), and nasopharyngitis (6.9%) were the three most commonly reported TEAEs in patients receiving gefurulimab, while headache (12.4%), diarrhoea (8.5%), and upper respiratory tract infections (7.8%) were more common among the placebo group.
Serious AEs were observed in 9.2% of patients in the gefurulimab group and 11.6% of patients in the placebo group. This included one death in each treatment arm, although neither death was deemed to be related to the intervention provided as part of the trial.
The researchers acknowledged that focusing on outcomes after six months meant they were unable to determine the longer-term safety and efficacy of gefurulimab.
“The OLE for PREVAIL is ongoing and is expected to provide evidence about the long-term clinical benefit and safety of gefurulimab,” they wrote. “During the RCT period, patients could continue previously prescribed MG medications provided the doses were stable and well tolerated. In the OLE, investigators may adjust the dose of concomitant medications.”
Associate Professor Christiane Schneider-Gold and Professor Ralf Gold, clinician-researchers with an interest in MG and other neurological conditions from Ruhr University Bochum in Germany, seemed cautiously optimistic about the results of the PREVAIL trial.
“Despite rather well-tolerated subcutaneous application, it remains an interesting matter which position gefurulimab will eventually gain in the continuously evolving treatment landscape in gMG and among the group of complement inhibitors,” the pair wrote in an accompanying editorial.
“It remains to be shown whether further nanobodies directed against other targets will follow in gMG therapy and for treatment of other neuroimmune diseases. Still, more highly effective therapeutics are needed in MG to increase the potential of reducing permanent disability in severely afflicted patients.”
JAMA Neurology, 27 July 2026 (manuscript)
JAMA Neurology, 27 July 2026 (editorial)
