Gefurulimab Cuts Hospitalizations and Sustains Response in Phase 3 PREVAIL Trial in Generalised Myasthenia Gravis
核心洞察
New PREVAIL analyses show gefurulimab reduced gMG-related hospitalization to 2.3% versus 9.3% with placebo and rescue therapy use to 5.3% versus 12.4%.
Median time to a 2-point or greater MG-ADL reduction was 1.3 weeks, with minimal symptom expression achieved by 44.3% of gefurulimab patients over 52 weeks.
Quality-of-life measures separated from placebo by week 4 and sustained through week 26, as gefurulimab advances through EU, US and China regulatory review.
New analyses from the phase 3 PREVAIL trial (NCT05556096) show that investigational gefurulimab (Klygefa; AstraZeneca) reduced gMG-related hospitalization and rescue therapy use versus placebo in adults with anti-acetylcholine receptor (搜索) antibody-positive generalized myasthenia gravis (搜索). In the 26-week randomized, double-blind period enrolling 260 patients (131 gefurulimab, 129 placebo), gMG-related hospitalization occurred in 3 patients (2.3%) on gefurulimab versus 12 (9.3%) on placebo (OR, 0.22; 95% CI, 0.06-0.81; P = .023), and rescue therapy was used by 7 (5.3%) versus 16 (12.4%) (OR, 0.39; 95% CI, 0.17-1.00; P = .049). Clinical deterioration occurred in 9 patients (6.9%) versus 18 (14.0%), a difference that did not reach statistical significance (OR, 0.45; 95% CI, 0.19-1.04; P = .061); gMG-related respiratory failure occurred in no gefurulimab-treated patients and 2 placebo patients (1.6%).
A second analysis covering the randomized period plus a 26-week open-label extension found a median time to a 2-point or greater MG-ADL reduction of 1.3 weeks and to a 3-point or greater reduction of 2.3 weeks; median time to a 3-point or greater QMG reduction was 4.3 weeks and to a 5-point or greater reduction 14.1 weeks. Response rates across extension assessments ranged from 72.2% to 85.7% for a 3-point or greater MG-ADL reduction and 48.4% to 58.5% for a 5-point or greater QMG reduction. Minimal symptom expression, defined as an MG-ADL score of 0 or 1, was reached by 58 of 131 patients (44.3%) at any point over 52 weeks, with a median cumulative duration of 25.9 weeks. Continuous gefurulimab maintained least squares mean changes from baseline of -5.3 points on MG-ADL, -5.3 points on QMG and -9.4 points on the Myasthenia Gravis Composite scale, with no meningococcal infections reported during the extension.
A third analysis of health-related quality of life in the same 260 patients found improvements with gefurulimab separated from placebo at week 4 on the MG-QOL15r and Neuro-QoL Fatigue Scale and at week 8 on the EQ-5D-5L, sustained through week 26. At week 26, least squares mean changes from baseline were -4.9 versus -2.3 (P = .0005) on the MG-QOL15r, -4.8 versus -2.5 (P = .0164) on Neuro-QoL Fatigue, 9.2 versus 4.6 (P = .0349) on the EQ-5D-5L VAS and 0.12 versus 0.04 (P = .0088) on the EQ-5D-5L health state index. The findings were presented at the 2026 AANEM Annual Meeting and MGFA Scientific Session. Gefurulimab was recommended for EU approval by the European Medicines Agency (搜索)'s Committee for Medicinal Products for Human Use earlier this month, with submissions under review in the United States, China and additional countries.