Cambridge, UK, 30 October 2025 – Alexion, AstraZeneca Rare Disease, today announced positive results from the global Phase III PREVAIL trial, showing that gefurulimab, a novel dual-binding nanobody, delivered statistically significant and clinically meaningful improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) at week 26 compared with placebo in adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Clinically meaningful benefits were observed as early as week one, underscoring gefurulimab’s potential to transform patient care through a convenient self-administered subcutaneous therapy.

Science Significance

The PREVAIL Phase III trial demonstrated the efficacy of gefurulimab, a next-generation complement C5 inhibitor engineered as a dual-binding nanobody. Its mechanism targets the terminal complement cascade to prevent immune-mediated neuromuscular damage, while its albumin-binding property extends half-life, enabling once-weekly dosing. Gefurulimab achieved a treatment difference of –1.6 points in MG-ADL total score versus placebo (95% CI: –2.4, –0.8; p<0.0001) at week 26. Early efficacy was evident from week one, sustained through the trial’s duration. Improvements in the Quantitative Myasthenia Gravis (QMG) total score were also significant by week four (treatment difference: –1.8; p<0.0001), continuing through week 26 (–2.1; p<0.0001). “These results support gefurulimab’s potential to deliver rapid, durable functional improvement in patients with gMG,” said Dr. Kelly Gwathmey, Chief of Neuromuscular Division at Virginia Commonwealth University and principal investigator for the study. “As a self-administered treatment, gefurulimab could offer both clinical benefit and convenience for patients managing a lifelong disease.”

Regulatory Significance

Gefurulimab has been granted Orphan Drug Designation in the US for the treatment of myasthenia gravis, highlighting its potential role in addressing a rare, high-burden autoimmune disorder. The PREVAIL data provide a robust clinical foundation to support regulatory submissions worldwide. The drug’s favorable safety profile, consistent with established C5 inhibitors eculizumab and ravulizumab, strengthens its case for approval. Most treatment-emergent adverse events (TEAEs) were mild to moderate, with injection-site reactions, headache, and back pain being the most common in gefurulimab-treated patients

Business Significance

Gefurulimab’s strong efficacy and self-administration profile position it as a potentially first-in-class subcutaneous complement inhibitor for gMG, expanding AstraZeneca’s rare disease leadership. According to Gianluca Pirozzi, Senior Vice President and Head of Development, Regulatory and Safety at Alexion, “Early and sustained complement inhibition with gefurulimab may translate into meaningful, functional improvement for patients. PREVAIL reflects Alexion’s dedication to advancing rigorous, patient-centered science.” The Phase III success also reinforces AstraZeneca’s strategy to diversify its rare disease portfolio and strengthen its biologics pipeline.

Patients’ Significance

Generalized myasthenia gravis affects approximately 85% of patients with AChR antibodies that disrupt neuromuscular communication. Symptoms can progress from drooping eyelids and slurred speech to life-threatening respiratory failure. For these patients, gefurulimab offers a new therapeutic option that combines rapid efficacy, durable control, and ease of use—potentially reducing hospital dependency and improving daily function. The once-weekly, subcutaneous regimen may lessen treatment burden, empowering patients with more autonomy in disease management.

Policy Significance

The success of PREVAIL highlights the growing importance of orphan drug development and patient-centric innovation in global health policy. With rare autoimmune diseases demanding specialized therapies, gefurulimab exemplifies how biopharmaceutical innovation can intersect with equitable access goals. Its progress may influence reimbursement frameworks and regulatory pathways for advanced biologics designed for home administration, aligning with broader healthcare efficiency initiatives.

Transaction Highlights

The PREVAIL (ALXN1720-MG-301) trial was a global, randomized, double-blind, placebo-controlled, parallel-group Phase III study that evaluated the safety and efficacy of gefurulimab in adults with generalized myasthenia gravis. The trial enrolled 260 participants across 20 countries spanning North America, Europe, Asia, and the Pacific region. Patients with confirmed AChR-Ab+ gMG (MGFA Class II–IV) were randomized 1:1 to receive either gefurulimab or placebo over a 26-week treatment period. Each participant received a single, weight-based loading dose on Day 1, followed by weekly maintenance dosing starting on Day 8.
Gefurulimab demonstrated statistically significant improvements in MG-ADL and QMG scores versus placebo, meeting all primary and secondary endpoints. The treatment showed a rapid onset of action and a sustained benefit through week 26. Importantly, the therapy was well-tolerated, with a safety profile consistent with other complement inhibitors. Participants completing the randomized period were offered enrollment into an open-label extension phase, which continues to evaluate the long-term safety and efficacy of gefurulimab as a self-administered subcutaneous therapy.

Source: AstraZeneca Press Release