Written By: Pallavi Sahane, BPharm
Reviewed By: Pharmacally Editorial Team
AstraZeneca’s novel dual-binding nanobody, Gefurulimab, has demonstrated statistically significant and clinically meaningful improvements in patients with generalized myasthenia gravis (gMG), in the latest results from the global, randomized, double-blind, placebo-controlled Phase III PREVAIL trial. The trial’s primary endpoint showed substantial improvement in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 26, with meaningful clinical benefit observed as early as week one. This milestone supports Gefurulimab potential as an effective, convenient, self-administered subcutaneous treatment for adults living with gMG. Alexion, AstraZeneca Rare Disease is a dedicated rare disease unit within AstraZeneca, specializes in novel therapies targeting the complement system and operates globally; headquartered in Boston, Massachusetts.
Clinical Evidence: Trial Design and Patient Population
The PREVAIL Phase III trial (NCT05556096) enrolled adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis, a rare and debilitating autoimmune disease characterized by severe muscle weakness and fatigue affecting patients’ ability to perform everyday activities like speaking, swallowing, and breathing. Participants were randomized to receive a weight-based loading dose of Gefurulimab on Day 1 followed by weekly subcutaneous maintenance doses starting Day 8, or placebo, for a treatment period of 26 weeks.
The primary endpoint is the change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score at week 26. Secondary endpoints included changes from baseline in the Quantitative Myasthenia Gravis (QMG) total score and the Myasthenia Gravis Composite (MGC) total score, both clinician-rated measures of disease severity.
Key Results
Gefurulimab met its primary efficacy endpoint by demonstrating a statistically significant 1.6-point greater reduction in MG-ADL total scores from baseline to week 26 compared to placebo. MG-ADL is a patient-reported measure assessing the impact of gMG symptoms on daily functioning. A clinically meaningful improvement was apparent as early as week one after treatment initiation, providing rapid symptom relief that was sustained throughout the study duration.
In addition to MG-ADL improvements, the trial showed significant benefit in the key secondary endpoint, the Quantitative Myasthenia Gravis (QMG) total score, a clinician-rated measure of disease severity. QMG scores improved by 1.8 points relative to placebo by week four, with sustained improvement reaching a 2.1 point reduction at week 26.
Safety and Tolerability
Gefurulimab was generally well tolerated with a safety profile consistent with other complement 5 (C5) inhibitors in gMG treatment. Most adverse events were mild or moderate and included injection site reactions, headache, and back pain, occurring at similar rates in both Gefurulimab and placebo groups. No new safety concerns emerged during the trial.
Key Opinions
Dr. Kelly Gwathmey, principal investigator of the trial highlighted the debilitating and fluctuating nature of gMG symptoms and noted that the trial results demonstrate early and sustained improvements in patient-reported and clinician-assessed outcomes, supporting Gefurulimab as an effective and convenient self-administered treatment option.
Gianluca Pirozzi Senior Vice President, Head of Development, Regulatory and Safety,, AstraZeneca stressed that the trial’s findings provide important insights into how early and continuous complement inhibition with Gefurulimab can translate into meaningful functional improvements. He also underscored the trial as one of the largest global studies in AChR-Ab+ gMG, reflecting the company’s commitment to rigorous, patient-centered science aimed at transforming care for this unpredictable disease worldwide.
AstraZeneca is now plans to present full data from the PREVAIL trial at upcoming medical congresses and intends to submit regulatory filings globally to seek approval. An open-label extension study is ongoing, allowing longer-term safety and efficacy assessment of Gefurulimab in gMG patients.
About Generalized Myasthenia Gravis
Generalized myasthenia gravis is a chronic autoimmune neuromuscular disease that impairs communication between nerves and muscles, resulting in profound muscle weakness. Symptoms often begin with drooping eyelids, double vision, or slurred speech, and can progress to life-threatening complications like respiratory failure if untreated.
About Gefurulimab
Gefurulimab (ALXN1720) is a humanized bispecific nanobody engineered by Alexion, AstraZeneca Rare Disease, specifically for the treatment of anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The drug’s patient-centric formulation allows for high-concentration, low-volume injections suitable for self-administration once per week, making it more convenient than existing intravenous C5 inhibitors.
Gefurulimab works by selectively binding to the complement protein C5, a key component of the terminal complement cascade involved in the immune attack on the neuromuscular junction in generalized myasthenia gravis (gMG). By binding to C5, Gefurulimab blocks its enzymatic cleavage into C5a and C5b, preventing the formation of the pro-inflammatory molecule C5a and the membrane attack complex (MAC, C5b-9). This inhibition halts complement-mediated inflammation and cell lysis at the neuromuscular junction, preserving muscle function and reducing disease symptoms.
References
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, AstraZeneca, 30 October 2025, https://www.astrazeneca.com/media-centre/press-releases/2025/positive-results-from-prevail-phase-iii-trial-at-aanem-mgfa-scientific-session.html
Safety and Efficacy of ALXN1720 in Adults with Generalized Myasthenia Gravis, ClinicalTrials.gov ID NCT05556096, https://clinicaltrials.gov/study/NCT05556096
James Howard et al, The Phase 3 PREVAIL Study Assessing the Efficacy and Safety of Subcutaneous Gefurulimab in Adults with Generalized Myasthenia Gravis: Trial in Progress (P7-11.021), Neurology, April 8, 2025 issue, 104 (7_Supplement_1) 1816, https://doi.org/10.1212/WNL.0000000000208763
Catalin J, et al. Clinical presentation of myasthenia gravis. Thymus. 2019. https://www.intechopen.com/chapters/67324