At AANEM 2026, Gefurulimab Cuts gMG Hospitalizations While Efgartigimod Data Broaden Myasthenia Gravis Coverage
核心洞察
Phase 3 PREVAIL analyses show gefurulimab reduced gMG-related hospitalization to 2.3% versus 9.3% with placebo (OR 0.22; 95% CI, 0.06-0.81; P=.023).
Gefurulimab-treated patients achieved a median 1.3 weeks to a 2-point or greater MG-ADL reduction, with 44.3% reaching minimal symptom expression over 52 weeks.
argenx reported deepening ocular MG responses with additional efgartigimod cycles and sustained one-year efficacy in anti-AChR antibody-negative generalized MG.
New analyses from the phase 3 PREVAIL trial (NCT05556096) show that investigational gefurulimab (Klygefa; AstraZeneca) reduced the risk of generalized myasthenia gravis (搜索) (gMG)-related hospitalization and rescue therapy use compared with placebo, while separate analyses found early, durable symptom improvement and quality-of-life gains through one year of treatment. The findings were presented at the 2026 AANEM Annual Meeting and MGFA Scientific Session, held September 29 to October 2 in Orlando, Florida.
argenx also presented data across its portfolio at the same meeting, including new efgartigimod results in ocular and antibody-negative MG, long-term CIDP data, and early-stage results for empasiprubart and adimanebart (搜索).
Gefurulimab and the PREVAIL Deterioration Analysis
One analysis assessed 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 (搜索) antibody-positive (AChR-Ab+) gMG (gefurulimab, n=131; placebo, n=129).
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).
Speed of 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, 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 Quantitative Myasthenia Gravis (QMG) score was 4.3 weeks, and to a 5-point or greater reduction was 14.1 weeks.
Response rates across open-label extension 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.
Separately, open-label extension safety and efficacy data 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.
Quality-of-Life Separation From Placebo
A third analysis evaluated health-related quality of life 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). 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.
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.
"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. "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."
Gefurulimab continues to advance through regulatory review. The drug was recommended for EU approval by the European Medicines Agency (搜索)'s Committee for Medicinal Products for Human Use earlier this month, and submissions remain under review in the United States, China, and additional countries.
Efgartigimod in Ocular and Antibody-Negative MG
argenx reported data from the phase 3 ADAPT OCULUS study showing that improvements in ocular MG among patients treated with VYVGART (efgartigimod alfa-fcab intravenously, and efgartigimod alfa plus hyaluronidase-qvfc subcutaneously as VYVGART Hytrulo) continue to deepen with additional treatment cycles. After two cycles beyond the placebo-controlled period, mean Myasthenia Gravis Impairment Index (MGII) patient-reported ocular scores improved further from -4.5 to -6.8 points in AChR-Ab-positive patients and from -2.7 to -4.5 points in triple-seronegative patients.
One-year ADAPT SERON results showed sustained efficacy and consistent safety in patients with generalized MG who do not have detectable anti-AChR antibodies, with mean MG-ADL improvements of approximately 5 points maintained through week 52. Real-world evidence from the German Myasthenia Gravis Registry found a higher disease burden among patients without detectable anti-AChR antibodies than among AChR-Ab-positive patients, including greater impairment in activities of daily living (mean MG-ADL 6.9 versus 4.8), disease severity, quality of life, and fatigue.
A real-world analysis of more than 1,100 U.S. MG patients treated with VYVGART showed improvements in MG-ADL scores, steroid burden and exacerbation rates across all sub-cohorts, with the greatest gains among patients who initiated treatment earlier, whether defined by fewer prior treatments or shorter time from diagnosis. Patients treated within a year of diagnosis had a mean MG-ADL reduction of 4.7 points over the first three months, versus 3.5 points among those treated more than three years after diagnosis, and 50% reached minimal symptom expression (p<0.001).
"The data we are presenting at AANEM and MGFA show how far the evidence for VYVGART now reaches, across years of treatment and into patient populations historically left out of clinical trials," said Luc Truyen, M.D., Ph.D., chief medical officer of argenx. "Our aim with VYVGART is to benefit as many patients as we can while simplifying treatment decisions for clinicians treating MG and CIDP. In MG, that means one clear treatment choice regardless of a patient's antibody status."
CIDP: Long-Term Safety, Grip Strength, and IVIg Transition
An interim analysis of the ADHERE and ADHERE+ studies reinforced the consistent safety profile of VYVGART Hytrulo with follow-up of CIDP patients extending beyond five years of treatment. On measures of disability, approximately 40% of responding participants reached an INCAT score of 0 or 1 during the extension, indicating independence in most daily activities with little to no functional disability.
A post hoc analysis showed VYVGART Hytrulo reduced the relative risk of grip strength deterioration in CIDP patients by 71.5% (hazard ratio 0.285; p<0.001), with early improvement detected faster through grip strength assessment than established disability measures.
Data from a phase 4 switch study evaluated the transition from IVIg to VYVGART Hytrulo one week after the last IVIg dose, with 87% of patients remaining on VYVGART Hytrulo through 12 weeks. A longitudinal analysis of ADHERE and ADHERE+ showed that 87.5% of treatment-naive patients treated with VYVGART Hytrulo achieved confirmed evidence of clinical improvement, and 44.4% of these patients improved by 2 or more INCAT points between the start of stage A and week 36 of ADHERE+.
Pipeline: Empasiprubart in MMN and Adimanebart in DOK7-CMS
Phase 2 ARDA+ results showed sustained clinical benefit and consistent safety with empasiprubart (ARGX-117) in multifocal motor neuropathy (搜索), supported by translational data on pathway-selective complement blockade. Empasiprubart is a humanized monoclonal antibody that binds C2 and blocks activation of both the classical and lectin pathways of the complement cascade, upstream of C3 and C5. In addition to MMN, argenx is evaluating empasiprubart in delayed graft function following kidney transplant and in CIDP.
The phase 1b study of adimanebart (搜索) (ARGX-119) in adults with DOK7-congenital myasthenic syndrome (搜索) reported in-clinic and real-world improvements in walking performance, measured by digital gait outcomes and informed by qualitative patient interviews. Adimanebart is a humanized agonist monoclonal antibody that targets and activates muscle-specific tyrosine kinase (搜索) (MuSK) to promote maturation and stabilization of the neuromuscular junction. DOK7 variations account for approximately 24% of CMS cases, and there are no approved treatments for the condition, which has an estimated prevalence of 5 per 1 million overall and 1.2 per 1 million for DOK7-CMS.
VYVGART is a first-in-class human IgG1 antibody fragment that binds to the neonatal Fc receptor (搜索) (FcRn), reducing circulating IgG autoantibodies. It is approved for gMG and, in Japan only, immune thrombocytopenia. VYVGART Hytrulo is approved for gMG and CIDP.