Weekly Gefurulimab Improves Daily Function in Generalized MG

Adults with generalized myasthenia gravis (gMG) who tested positive for anti-acetylcholine receptor antibodies (AChR-Ab+) showed greater gains in daily functioning with self-injected gefurulimab (Klygefa; Alexion, AstraZeneca Rare Disease) once a week than with a placebo, according to results from the phase 3 PREVAIL trial (NCT05556096) published in JAMA Neurology.¹ At week 26, the least-squares mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score fell by 4.2 points with gefurulimab vs 2.6 points with placebo.

The MG-ADL benefit was evident after 1 week of dosing, and the clinician-rated Quantitative Myasthenia Gravis (QMG) scores differed by week 4 in the treatment vs placebo group. Rates of adverse events (AEs) were similar between arms, and no meningococcal infections were reported.

Complement Inhibition and Treatment Options in Generalized Myasthenia Gravis

Roughly 85% of patients with gMG have autoantibodies targeting the AChR on skeletal muscle.^1,2 Antibody binding activates complement, and once complement component 5 (C5) is cleaved, the resulting membrane attack complex can injure the postsynaptic membrane and disrupt neuromuscular signaling, the authors explained. Approved C5 inhibitors include intravenous eculizumab (Bkemv; Amgen) and ravulizumab (Ultomiris; Alexion, AstraZeneca Rare Disease), given every 2 and 8 weeks, respectively, and daily subcutaneous zilucoplan (Zilbrysq; UCB). Other options include neonatal Fc receptor blockers and B-cell depletion, but the authors argued that patients could benefit from more administration choices.

Topline PREVAIL results announced in July 2025 showed the trial met its primary and all secondary end points.³

The double-blind trial ran at 113 sites in 20 countries. Over a 2-year enrollment window ending in November 2024, investigators randomly assigned 260 adults with AChR-Ab+ gMG, Myasthenia Gravis Foundation of America class II to IV disease, and an MG-ADL score of 5 or higher to gefurulimab (n = 131) or placebo (n = 129). Patients or caregivers used a prefilled syringe to give a weight-based loading dose of 600 or 900 mg on day 1, then weekly maintenance doses of 300 or 600 mg through week 26. Participants had a mean age of 52.8 (15.73) years, and stable background corticosteroids or nonsteroidal immunosuppressants were allowed. In all, 249 patients (95.8%) finished the controlled period.

Gefurulimab Improves MG-ADL, QMG Scores in gMG

The week 26 difference in MG-ADL scores—the primary end point—was −1.6 points (95% CI, −2.4 to −0.8; P < .001). On the key secondary end point, QMG scores dropped 4.5 points with gefurulimab compared with 2.4 points with placebo (difference, −2.1; 95% CI, −3.1 to −1.1; P < .001). Myasthenia Gravis Composite scores improved by 7.8 vs 4.7 points (difference, −3.1; 95% CI, −4.4 to −1.7; P < .001).

A total of 58 of 124 patients (46.8%) had a QMG reduction of at least 5 points in the gefurulimab arm and 33 of 118 (28.0%) in the placebo arm (OR, 2.56; 95% CI, 1.42-4.62; P = .002). An MG-ADL reduction of at least 3 points was seen in 82 of 125 (65.6%) and 63 of 121 (52.1%), respectively (OR, 1.74; 95% CI, 1.03-2.93; P = .04). Seven patients (5.3%) receiving gefurulimab and 16 (12.4%) receiving placebo used rescue therapy.

“These results confirm clinically meaningful improvements in both patient-reported (MG-ADL) and investigator-assessed (QMG) outcome measures,” the authors wrote. They added that the MG-ADL effect fell within the range reported in phase 3 trials of other advanced gMG therapies, while cautioning that differences in design limit such comparisons.

Any AE was reported in 99 patients (75.6%) receiving gefurulimab and 104 (80.6%) receiving placebo, and most were mild or moderate. Injection site reactions were more frequent with gefurulimab (13 [9.9%] vs 4 [3.1%]), usually first appearing within 3 weeks, and no one left the trial due to an injection site reaction. Serious AEs affected 12 patients (9.2%) and 15 patients (11.6%), respectively. None in the gefurulimab arm were considered treatment related, and neither of the 2 deaths (1 per group) was attributed to the study drug.

The authors acknowledged that 6 months of randomized data are not enough to judge long-term safety and efficacy, and they pointed to the ongoing open-label extension, which runs up to 202 weeks, to fill that gap. They also noted that Black or African American patients were underrepresented, making up 6 of 260 participants (2.3%).

In September 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended approving gefurulimab as add-on therapy for adults with AChR-Ab+ gMG. The drug is approved in Japan and under review in the US and China.²

“With the advantage of self-administered subcutaneous weekly dosing, gefurulimab has the potential to offer patients with AChR-Ab+ gMG an effective and convenient option,” the authors concluded.

References

1. Gwathmey KG, Saccà F, Howard JF Jr, et al; PREVAIL Trial Investigators. Efficacy and safety of gefurulimab in generalized myasthenia gravis: the PREVAIL phase 3 randomized clinical trial. JAMA Neurol. 2026;83(9):841-850. doi:10.1001/jamaneurol.2026.2333

2. Klygefa (gefurulimab) recommended for approval in the EU by CHMP for the treatment of adults with generalised myasthenia gravis (gMG). News release. AstraZeneca. September 21, 2026. Accessed October 30, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/klygefa-recommended-for-approval-in-the-eu.html

3. Gefurulimab dual-binding nanobody demonstrated statistically significant and clinically meaningful improvement in functional activities of daily living in adults with generalised myasthenia gravis in PREVAIL phase III trial. News release. AstraZeneca. July 24, 2025. Accessed October 30, 2026. https://www.astrazeneca.com/media-centre/press-releases/2025/gefurulimab-nanobody-met-phase-iii-endpoints.html