Peer-reviewed PREVAIL Phase 3 results published in JAMA Neurology show gefurulimab significantly improved generalized myasthenia gravis with weekly self-injection.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Nearly nine months after AstraZeneca reported positive top-line findings from the Phase III PREVAIL trial in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab+ gMG), the complete peer-reviewed results have been published in JAMA Neurology, confirming that weekly self-administered gefurulimab produced rapid and sustained improvements in disease severity while providing comprehensive efficacy, safety, and responder analyses.
Complement Inhibition Targets a Key Disease Mechanism
Generalized myasthenia gravis is a chronic autoimmune neuromuscular disorder in which antibodies against the acetylcholine receptor activate the complement cascade, leading to destruction of the neuromuscular junction and progressive muscle weakness.
Gefurulimab is a novel dual-binding nanobody that blocks complement component 5 (C5), preventing terminal complement activation. Unlike conventional monoclonal antibodies, the molecule incorporates an albumin-binding domain that extends its half-life, allowing once-weekly subcutaneous self-injection. This approach combines complement inhibition with a more convenient administration schedule than existing intravenous therapies.
Unlike intravenous C5 inhibitors such as eculizumab and ravulizumab, gefurulimab is administered as a low-volume once-weekly subcutaneous self-injection, offering a more convenient treatment option that may reduce treatment burden for patients.
PREVAIL Trial Met All Primary and Secondary Endpoints
PREVAIL (NCT05556096) was a randomized, double-blind, placebo-controlled Phase 3 trial conducted across 113 centers in 20 countries. The study enrolled 260 adults with AChR-Ab+ generalized myasthenia gravis classified as Myasthenia Gravis Foundation of America (MGFA) class II to IV and an MG-ADL score of at least five.
Participants were randomized to receive weekly weight-based subcutaneous gefurulimab or placebo for 26 weeks while continuing stable background therapies when appropriate. The primary endpoint evaluated change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, while the key secondary endpoint assessed the Quantitative Myasthenia Gravis (QMG) score.
Gefurulimab produced clinically meaningful improvements across multiple efficacy measures:
- MG-ADL score: Least-squares mean improvement of −4.2 versus −2.6 with placebo, yielding a treatment difference of −1.6 (95% CI, −2.4 to −0.8; P < .001).
- QMG score: Improvement of −4.5 versus −2.4, corresponding to a treatment difference of −2.1 (95% CI, −3.1 to −1.1; P < .001).
- Symptom improvement appeared rapidly, with MG-ADL benefits observed within one week and QMG improvements by week four, remaining consistent through week 26.
- Nearly 46.3% of treated patients achieved at least a five-point reduction in QMG compared with 25.2% receiving placebo, while 65.5% achieved at least a three-point reduction in MG-ADL versus 52.2% in the placebo group.
Patients receiving gefurulimab also required rescue therapy less frequently than those receiving placebo (5.3% versus 12.4%).
Favorable Safety Profile Supports Long-Term Development
Treatment-emergent adverse events occurred at similar rates in both study groups, affecting 75.6% of patients receiving gefurulimab and 80.6% receiving placebo. Most events were mild to moderate.
The most frequently reported adverse events with gefurulimab included injection-site reactions, headache, back pain, and nasopharyngitis. Injection-site reactions generally occurred during the first few weeks of therapy and declined over time, with no treatment discontinuations attributed to these events.
Importantly, no meningococcal infections were reported, a notable consideration for complement inhibitor therapy. Serious adverse events occurred in 9.2% of the gefurulimab group and 11.6% of the placebo group, with no new safety signals identified.
Investigators Highlight Early Clinical Benefit
The investigators concluded that gefurulimab demonstrated rapid onset, durable efficacy, and a safety profile comparable to established complement inhibitors while offering the practical advantage of once-weekly self-administration.
They also noted that the nanobody platform enables low-volume subcutaneous dosing, potentially providing patients with greater treatment flexibility and independence compared with intravenous complement inhibitors.
Future Development
The randomized treatment period has transitioned into an ongoing open-label extension expected to continue for up to 202 weeks. Long-term follow-up will evaluate the durability of clinical benefit, long-term safety, and the potential for adjustment of background immunosuppressive therapies.
If confirmed in the extension study, gefurulimab could become the first nanobody-based neurological therapy targeting complement C5, expanding treatment options for patients with AChR-Ab+ generalized myasthenia gravis.
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About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.