Phase 3 PREVAIL Results: Gefurulimab Displays Efficacy in AChR-Positive Generalized Myasthenia Gravis

Results from the global, randomized, double-blind, placebo-controlled study phase 3 PREVAIL trial (NCT05556096) showed that subcutaneous, self-administered gefurulimab met primary and secondary efficacy endpoints in adults with acetylcholine receptor antibody–positive (AChR-Ab+) generalized myasthenia gravis (gMG).¹

Presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, help April 18-22, in Chicago, Illinois, Gefurulimab demonstrated statistically significant and clinically meaningful improvements in disease-specific outcome measures, including the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, with effects observed as early as week 1 and sustained through 26 weeks.¹ All told, these data suggest that a self-administered complement inhibitor may offer a more convenient alternative to currently available intravenous therapies.

Trial Overview and Key Findings

Led by Kelly Gwathmey, MD, associate professor of neurology and chief of Neuromuscular Division at Virginia Commonwealth University, PREVAIL is a global phase 3 trial evaluating the efficacy and safety of gefurulimab, a dual-binding nanobody targeting complement component 5 (C5), in adults with AChR-Ab+ gMG.² A total of 260 participants were randomized 1:1 to receive weekly subcutaneous gefurulimab (n = 131) or placebo (n = 129).¹

The primary endpoint—change from baseline in MG-ADL total score at week 26—was met, with a least squares mean (LSM) reduction of –4.2 in the gefurulimab group compared with –2.6 in the placebo group (treatment difference, –1.6; standard error of the mean [SEM], 0.40; P <.0001).¹

Secondary endpoints were also achieved. At week 26, patients receiving gefurulimab demonstrated greater improvements in Quantitative Myasthenia Gravis (QMG) scores (–4.5 vs –2.4; treatment difference, –2.1; P<.0001) and Myasthenia Gravis Composite (MGC) scores (–7.8 vs –4.7; treatment difference, –3.1; P<.0001) compared with placebo.¹

Notably, improvements were observed early in the treatment course, with MG-ADL changes evident by week 1 and QMG and MGC improvements by week 4.¹ Additionally, safety findings were broadly comparable between groups, with no notable differences in adverse events and no reported cases of meningococcal infection.¹

Interpretation and Limitations

The PREVAIL results reinforce the role of complement inhibition in improving clinical outcomes in AChR-Ab+ gMG. The magnitude of improvement across MG-ADL, QMG, and MGC scores is generally consistent with prior studies of C5 inhibitors.^2,3

However, several considerations remain. Detailed safety data, including rates of serious infections and long-term outcomes, were not fully reported. In addition, while no meningococcal infections were observed, complement inhibition is associated with an increased risk of such infections, necessitating vaccination and monitoring in clinical practice.²

Further data will be needed to determine how gefurulimab compares directly with existing therapies, particularly with respect to durability of response, safety, and patient-reported outcomes.

Drug Background and Previous Studies

Gefurulimab is an investigational, dual-binding nanobody designed to inhibit complement component C5, thereby preventing formation of the membrane attack complex and reducing neuromuscular junction damage.¹ Nanobody-based therapies are engineered to be smaller and potentially more stable than conventional monoclonal antibodies, which may facilitate subcutaneous delivery and self-administration.

Prior to PREVAIL, gefurulimab was studied in a phase 1 trial of healthy volunteers, primarily to assess pharmacokinetics and safety profile. The trial featured patients aged 18-45 who were randomly assigned 3:1 to either gefurulimab or placebo, for a period of 7 weeks. The data, presented at the 2023 AAN annual meeting, showed that the therapy was well tolerated, with no serious adverse events reported.⁵

Read more: Complement Inhibitor Gefurulimab Meets End Points in Phase 3 PREVAIL Study of Myasthenia Gravis

In the study, patients received either subcutaneous gefurulimab as a single dose (30-1700 mg), multiple doses (100 or 300 mg) once weekly for 3 weeks, or a single dose of intravenous gefurulimab. Overall, serum exposure increased dose dependently over 3 weekly doses of 100 mg and 300 mg, and single doses of at least 100 mg with extended multiple dosing achieved complete terminal complement inhibition (serum free C5 < 0.5 µg/mL). Low-titer, treatment-emergent (TE) anti-drug antibodies were observed in 12% (9/73) of participants who received gefurulimab.⁵

Clinical Context and Next Steps

Standard treatment for generalized myasthenia gravis includes acetylcholinesterase inhibitors, corticosteroids, and other immunosuppressive therapies. However, many patients experience persistent symptoms or treatment-related adverse effects, highlighting the need for targeted therapies.

Complement inhibition has emerged as an effective strategy in this setting. Agents targeting C5, including Eculizumab and Ravulizumab, have demonstrated efficacy in AChR-Ab+ gMG and are approved in multiple regions.^2,3 These therapies, however, require intravenous administration, which may limit convenience and accessibility for some patients.

Additional analyses from PREVAIL, including subgroup evaluations and longer-term follow-up, are expected to further define the clinical profile of gefurulimab. Regulatory submissions will determine whether subcutaneous complement inhibition becomes a new option for patients with gMG.

REFERENCES
1. Gwathmey K, Sacca F, Howard JF Jr, et al. Efficacy and safety of subcutaneous self-administeredgefurulimab in generalized myasthenia gravis: primary results fromthe phase three, randomized, double-blind,placebo-controlled PREVAIL study. Presented at: 2026 American Academy of Nerurology Annual Meeting; April 18-22, 2026, Chicago, Illionis.
2. Howard JF Jr, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16(12):976-986. doi:10.1016/S1474-4422(17)30369-1.
3. Vu TH, Mantegazza R, Annane D, et al. Long-Term Efficacy and Safety of Ravulizumab in Adults With Anti-Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: Final Results From the Phase 3 CHAMPION MG Open-Label Extension. Eur J Neurol. 2025;32(4):e70158. doi:10.1111/ene.70158
4. Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016;375(26):2570-2581. doi:10.1056/NEJMra1602678.
5. Ortiz S, McEneny A, Amancha P, et al. Safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of subcutaneous and intravenous ALXN1720 in healthy volunteers: a phase 1, randomized, double-blind, placebocontrolled, single and multiple ascending dose study. Presented at: 2023 AAN Annual Meeting. ABSTRACT P1-5.016