Gefurulimab for MG Exhibits Lasting Efficacy, Safety in Topline PREVAIL Trial Data

Over 26 weeks, the complement C5 inhibitor gefurulimab showed its ability to produce statistically significant improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score, a clinically meaningful result, as well as reduce Quantitative Myasthenia Gravis (QMG) total scores at week 4 and week 26.¹ These new top-line results from the phase 3, randomized, double-blind, placebo-controlled PREVAIL study (NCT05556096) were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting by Kelly G. Gwathmey, MD, associate professor at Virginia Commonwealth University (VCU) School of Medicine, director of the VCU amyotrophic lateral sclerosis clinic, and Division of Neuromuscular chief. She is also principal investigator of PREVAIL.

Compared with conventional monoclonal antibodies, which typically require intravenous infusion by a health care professional, gefurulimab has the added convenience of being available as a prefilled syringe or autoinjector, Gwathmey explained. Gefurulimab is administered subcutaneously, with its low molecular weight and ability to extend the half-life of albumin—its dual-binding activity blocks C5 activation and binds to the liver-produced protein—key to its weekly administration.²

The adult patients evaluated in PREVAIL had anti-acetylcholine receptor (AChR) antibody-positive (Ab+) generalized myasthenia gravis (gMG).¹ They also had to have Myasthenia Foundation of America (MGFA) class II-IV disease, an MG-ADL score of 5 or higher, and be stable on standard-of-care therapy. They were randomized 1:1 to self-administered weekly gefurulimab (n = 131) or placebo (n = 129) for 25 weeks. The primary end point is change from baseline in MG-ADL total score at week 26, and the secondary end point is change from baseline in QMG total score at week 26. Most patients were female (59.5% who received gefurulimab, 61.2% who received placebo), older than age 50 at first dose, age 43 at first clinical presentation of MG, and a White race (52.7% and 57.4%, respectively).

Overall, most patients had MGFA class II disease (36.6% and 34.9%) or class III disease (58.0% and 59.7%), mean (SD) MG duration of 9.2 (8.45) and 8.2 (8.79) years, mean MG-ADL score of 9.0 years (across both groups), and mean QMG score of 14.9 (4.38) or 14.7 (4.39). The least squares mean (LSM) change in MG-ADL was –4.2 (0.29) from gefurulimab and –2.6 (0.27) from placebo, for a treatment difference of –1.6 (0.40) (95% CI, –2.4 to –0.8; P < .0001). The early MG-ADL score improvement seen in week 1 after the loading dose was sustained through week 26.

For QMG change, the treatment difference seen by week 4 (LSM, –1.8 [0.37]; 95% CI, –2.5 to –1.1; P < .0001) rose through week 26 (LSM, –2.1 [0.50]; 95% CI, –3.1 to –1.1; P < .0001). As with the treatment cohort, the improvement first seen at week 4 was sustained through week 26.

“People living with gMG face fluctuating and often debilitating symptoms, including loss of muscle function and severe weakness, Gwathmey said in a statement.² “Results from the PREVAIL phase 3 trial demonstrating early and lasting benefits in MG-ADL and QMG scores support the potential for gefurulimab to offer an efficacious and convenient self-administered treatment option that may help address the unpredictability of this disease.”

Treatment-emergent adverse events were typically injection site reactions (9.9%), headache (9.9%), and back pain (7.6%) among the gefurulimab group and headache (12.4%), diarrhea (8.5%), and upper respiratory tract infection (7.8%) among the placebo group. There were more TEAEs in the gefurulimab vs the placebo group (75.6% vs 80.6%), but these rates were considered similar overall.

Of the patients from the original PREVAIL treatment group, 4 discontinued treatment during the study, and all remaining 127 patients entered the open-label extension (OLE) analysis, which is investigating gefurulimab over a maximum of 202 weeks. Of the placebo group, 7 discontinued treatment and all remaining 122 patients entered the OLE analysis.

“Based on these clinical benefits and the advantage of self-administered [subcutaneous] weekly dosing,” the study authors concluded,” gefurulimab may offer patients with AChR-Ab+ gMG a convenient and effective treatment option.”

References

1. Gefurulimab demonstrates statistically significant and clinically meaningful improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) at week 26 with clinically meaningful improvement seen as early as week one in adults with gMG in PREVAIL phase III trial. News release. AstraZeneca. October 30, 2025. Accessed November 7, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/positive-results-from-prevail-phase-iii-trial-at-aanem-mgfa-scientific-session.html
2. Efficacy and safety of subcutaneous self-administered gefurulimab in generalized myasthenia gravis: topline results from a phase 3, randomized, double-blind, placebo-controlled study (PREVAIL). Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting; October 29-November 1, 2025; in San Francisco, California.