Novel Nanobody Shows Promise in Myasthenia Gravis

Weekly injections of the novel dual-binding nanobody gefurulimab were associated with a reduced need for rescue therapy, numerically less clinical deterioration, and fewer hospitalizations among patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG).Nicholas S. Streicher, MDNew phase 3 data suggest that the novel complement component 5 (C5) inhibitor may offer rapid and sustained disease control and provide another treatment option for patients with persistent symptoms, study investigator Nicholas S. Streicher, MD, assistant professor of neurology at Georgetown University in Washington, DC, told Medscape Medical News.The findings were presented on September 29 at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2026.A Novel Approach to C5 InhibitiongMG is a rare autoimmune neuromuscular disorder characterized by fluctuating muscle weakness that can significantly impair daily functioning. Symptoms include slurred speech, double vision, drooping eyelids, and weakness in the arms and legs, which may worsen with activity and vary in severity over time.Approximately 85% of patients with gMG are positive for anti-AChR antibodies, which bind to AChRs at the neuromuscular junction, disrupting nerve-to-muscle signaling and triggering an immune response that damages the junction. Gefurulimab is a “nanobody,” which Streicher said is similar to an antibody but smaller in size. It inhibits the activation of C5, a key driver of disease in anti-AChR antibody-positive gMG. “It works by shutting down the part of the immune system that ultimately destroys the physical space where nerve and muscle transmission happens,” he noted. The multicenter, phase 3, double-blind PREVAIL trial enrolled 260 adults with anti-AChR antibody-positive gMG who had Myasthenia Gravis Foundation of America class II-IV disease and a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 and were receiving stable standard-of-care treatment.The participants had a mean age of 52.8 years; 60.4% of the participants were female, and approximately 55% were White. All were randomly assigned to receive gefurulimab or placebo for 26 weeks, administered as weekly subcutaneous self-injections using a prefilled syringe or autoinjector. The mean baseline MG-ADL total score was 9 in both treatment groups, and nearly all participants (94.6%) completed the 26-week treatment.As previously reported in JAMA Neurology, the trial met its primary endpoint of change from baseline in MG-ADL total score at week 26, with a least-squares mean reduction of 4.2 points in the gefurulimab group vs 2.6 points in the placebo group (between-group difference, -1.6 points; 95% CI, -2.4 to -0.8; P < .001).Gefurulimab was generally well tolerated, with a safety profile consistent with that observed in previous trials of C5 inhibitors in gMG and no new safety signals being identified.Clinical deterioration was defined as worsening gMG signs or symptoms resulting in an increase of at least three points in the MG-ADL total score or at least two points in any individual MG-ADL item or gMG-related weakness severe enough to require intubation or delay extubation. It occurred in nine patients (6.9%) in the gefurulimab group vs 18 (14.0%) in the placebo group (odds ratio [OR], 0.445; 95% CI, 0.191-1.038; P = .0610). “The drug was better — 14% vs 7% — but there wasn’t a statistically significant difference,” noted Streicher. Fewer Hospitalizations, Less Rescue TherapyAnother exploratory outcome was the need for rescue therapy, which could include high-dose corticosteroids, plasmapheresis or plasma exchange, or intravenous immunoglobulin (IVIG). Rescue therapy was administered when clinical deterioration occurred or when a patient’s health was at risk without urgent intervention. Rescue therapy was required in seven (5.3%) patients in the gefurulimab group vs 16 (12.4%) patients in the placebo group (odds ratio [OR], 0.394; 95% CI, 0.155-0.995; P = .0491).A third exploratory outcome was gMG-related hospitalization at 26 weeks, which occurred in three (2.3%) patients in the gefurulimab group vs 12 (9.3%) patients in the placebo group (OR, 0.221; 95% CI, 0.060-0.812; P = .0229).The reduced need for rescue therapy and fewer hospitalizations “shows exactly how well this drug is working,” Streicher said. “The idea is that you could potentially start reducing steroids, which have their own negative health effects as time goes on.”Gefurulimab may offer several advantages over existing therapies, including the convenience of subcutaneous self-administration rather than intravenous infusion and the potential for use alongside other treatments, Streicher said.Unlike conventional antibodies, which may be cleared from the body during treatments with agents such as IVIG, gefurulimab is designed to remain effective, potentially allowing it to be used in combination with other therapies, he explained.The drug is currently under review by the FDA.Streicher reported being a site investigator for PREVAIL and having a research relationship with Alexion, AstraZeneca Rare Disease, the developer of gefurulimab. He also reported serving as a paid speaker and consultant for Amgen and as an internal speaker and consultant for Immunovant, Amgen, and AstraZeneca. The study was funded by Alexion, AstraZeneca Rare Disease.