Gefurulimab Cuts Hospitalizations, Sustains Response in Phase 3 PREVAIL Trial of Myasthenia Gravis

New analyses from the phase 3 PREVAIL trial (NCT05556096) showed that investigational gefurulimab (Klygefa; AstraZeneca) reduced the risk of generalized myasthenia gravis (gMG)-related hospitalization and rescue therapy use compared with placebo, while separate analyses found early, durable symptom improvement and quality-of-life gains through 1 year of treatment. These findings were presented at the 2026 AANEM Annual Meeting and MGFA Scientific Session, held September 29 to October 2 in Orlando, Florida.¹

Clinical deterioration, rescue therapy, and hospitalization

One analysis assessed the incidence of protocol-defined clinical deterioration, gMG-related hospitalization, and rescue therapy use during PREVAIL's 26-week randomized, double-blind, placebo-controlled period which enrolled 260 adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) gMG (gefurulimab, n = 131; placebo, n = 129.^2,5

Overall, clinical deterioration occurred in 9 patients (6.9%) receiving gefurulimab versus 18 (14.0%) receiving placebo, a difference that did not reach statistical significance (odds ratio [OR], 0.45; 95% CI, 0.19-1.04; P =.061); gMG-related respiratory failure occurred in none of the gefurulimab-treated patients and in 2 (1.6%) of the placebo-treated patients.

Rescue therapy, which could include plasma exchange, intravenous immunoglobulin, or high-dose corticosteroids, was used by 7 patients (5.3%) on gefurulimab versus 16 (12.4%) on placebo (OR, 0.39; 95% CI, 0.17-1.00; P =.049). 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).²

Time to response and minimal symptom expression

A second analysis followed patients through 52 weeks, combining the 26-week randomized period with a 26-week open-label extension (OLE), to evaluate how quickly gefurulimab-treated patients responded. Among 131 patients randomized to gefurulimab, median time to a 2-point or greater reduction in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score was 1.3 weeks, and to a 3-point or greater reduction was 2.3 weeks; median time to a 3-point or greater reduction in QMG score was 4.3 weeks, and to a 5-point or greater reduction was 14.1 weeks.³

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Response rates across OLE assessments ranged from 72.2% to 85.7% for a 3-point or greater MG-ADL reduction and from 48.4% to 58.5% for a 5-point or greater QMG reduction. Minimal symptom expression (MSE), defined as an MG-ADL score of 0 or 1, was achieved by 58 of 131 patients (44.3%) at any point during the 52 weeks, with a median cumulative duration of 25.9 weeks.

“Through 52 weeks in PREVAIL, gefurulimab treatment resulted in early onset of clinically meaningful responses and durable MSE,” Alexis Lizarraga, MD, adjunct associate professor of neurology in the neuromuscular medicine division at the University of Rochester Medical Center, and colleagues concluded.³

Separately, OLE safety and efficacy data presented in the same release showed that patients receiving continuous gefurulimab maintained functional improvements through 52 weeks, building on the trial's 26-week primary results: 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. No meningococcal infections were reported during the extension.¹

Health-related quality of life

A third analysis evaluated health-related quality of life (HRQoL) outcomes among the same 260 randomized patients using the MG-QOL 15-Item Questionnaire-Revised (MG-QOL15r), the Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Scale, and the EuroQol-5 Dimensions-5-Level (EQ-5D-5L) visual analogue scale (VAS) and health state index (HSI). All told, improvements with gefurulimab separated from placebo starting at week 4 on the MG-QOL15r and Neuro-QoL Fatigue measures and at week 8 on the EQ-5D-5L, sustained through week 26.⁴

At week 26, least squares mean changes from baseline among patients with available data were -4.9 versus -2.3 (P =.0005) on the MG-QOL15r, -4.8 versus -2.5 (P =.0164) on the Neuro-QoL Fatigue scale, 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 HSI, favoring gefurulimab over placebo on each measure.⁴

“Alexion's robust data at the AANEM and MGFA Scientific Session reinforce how we continue to pioneer new possibilities to advance gMG care and deliver on our commitment to this community,” Christophe Hotermans, senior vice president and head of global medical affairs at Alexion, said in a statement.¹ “Together with new analyses from the PREVAIL trial showing reduced risks of gMG-related hospitalizations and rescue therapy use, these data further demonstrate the potential for gefurulimab to be a convenient self-administered treatment option that can deliver rapid and sustained disease control for people living with this unpredictable rare disease.”

The findings arrive as gefurulimab continues to advance through regulatory review; the drug was recommended for EU approval by the European Medicines Agency's Committee for Medicinal Products for Human Use earlier this month, and submissions remain under review in the United States, China, and additional countries.⁶

REFERENCES
1. Alexion advances pioneering leadership in gMG care with data at 2026 AANEM Annual Meeting and MGFA Scientific Session. News release. Published September 24, 2026. Accessed September 25, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/alexion-advances-pioneering-leadership-in-gmg-care-with-data-at-2026-aanem-annual-meeting-and-mgfa-scientific-session.html
2. Winkley J, Govindarajan R, Streicher N, Gialdini G, Shang S, Rakhade S, Annane D. Clinical deterioration, rescue therapy, and hospitalization among patients with generalized myasthenia gravis (gMG): results from the PREVAIL trial of gefurulimab. Presented at: 2026 AANEM Annual Meeting and MGFA Scientific Session; September 29-October 2, 2026; Orlando, FL.
3. Lizarraga A, Dimachkie M, Shin HY, Shang S, Rakhade S, Maurer M. Time to response and minimal symptom expression with gefurulimab in generalized myasthenia gravis (gMG): 52-week results from the phase 3 PREVAIL trial. Presented at: 2026 AANEM Annual Meeting and MGFA Scientific Session; September 29-October 2, 2026; Orlando, FL.
4. Ruck T, Sacca F, Vu T, Rakhade S, Racine A, Pandeya S, Lizarraga A. Health-related quality of life in patients with generalised myasthenia gravis receiving gefurulimab in the PREVAIL trial. Presented at: 2026 AANEM Annual Meeting and MGFA Scientific Session; September 29-October 2, 2026; Orlando, FL.
5. A study to evaluate gefurulimab in adult participants with generalized myasthenia gravis (PREVAIL). ClinicalTrials.gov identifier: NCT05556096. Accessed September 25, 2026. https://clinicaltrials.gov/study/NCT05556096
6. Klygefa (gefurulimab) recommended for approval in the EU by CHMP for the treatment of adults with generalised myasthenia gravis (gMG). News release. Published September 18, 2026. Accessed September 25, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/klygefa-recommended-for-approval-in-the-eu.html