MATCHING-ADJUSTED INDIRECT COMPARISON OF ZILUCOPLAN VERSUS CEMDISIRAN AND GEFURULIMAB IN GENERALISED MYASTHENIA GRAVIS (GMG)
Author(s)
Vikalp Maheshwari, PGDM1, Aakanksha Jaiswal, BSc, MSc1, Sudarshan Tewary, M.Sc1, April Betts, PhD2.
1Parexel International, Hyderabad, India, 2UCB, Slough, United Kingdom.
1Parexel International, Hyderabad, India, 2UCB, Slough, United Kingdom.
OBJECTIVES: Comparative evidence across complement-targeted therapies in generalized myasthenia gravis (gMG) is limited by the absence of direct trials. Understanding comparative efficacy within the C5 inhibitor class is important to inform treatment decisions. This study evaluated zilucoplan versus cemdisiran and gefurulimab at 24 weeks.
METHODS: Trials were identified via systematic literature review. Individual patient data from RAISE (zilucoplan) were reweighted to match baseline characteristics of cemdisiran (NIMBLE) and gefurulimab (PREVAIL) trial populations. Because no common comparator was available at Week 24, unanchored MAICs were performed. Feasibility was assessed via eligibility/baseline comparisons and overlap diagnostics. Endpoints at 24 weeks were MG-ADL response (≥3-point improvement) and QMG response (≥5-point improvement). For gefurulimab, the closest assessment was Week 26 to compare with Week 24 outcomes from RAISE. Effects were summarized as odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS: Base-case weighting achieved acceptable stability with effective sample size (ESS)=59 vs cemdisiran and ESS=66 vs gefurulimab; weight ranges were 0.14-3.42 and 0.21-2.47, respectively. In base-case analyses, zilucoplan showed statistically significant improvements in QMG response versus both comparators, while MG-ADL response was significant vs gefurulimab only. Versus cemdisiran, MG-ADL response OR was 2.01 (95% CI 0.70-5.73) and QMG response OR was 4.08 (95% CI 1.74-9.58). Versus gefurulimab, MG-ADL response OR was 3.92 (95% CI 1.62-9.48) and QMG response OR was 4.08 (95% CI 1.97-8.45). Sensitivity analyses were directionally consistent.
CONCLUSIONS: Zilucoplan demonstrated superior comparative efficacy versus gefurulimab for QMG and MG-ADL responses, and statistically significant improvements in QMG response versus cemdisiran. The studies had significant baseline differences and although efforts were made to adjust, residual confounding might remain. Whilst acknowledging uncertainty, these findings provide an indication of superior comparative efficacy of zilucoplan compared with cemdisiran, and gefurulimab.
METHODS: Trials were identified via systematic literature review. Individual patient data from RAISE (zilucoplan) were reweighted to match baseline characteristics of cemdisiran (NIMBLE) and gefurulimab (PREVAIL) trial populations. Because no common comparator was available at Week 24, unanchored MAICs were performed. Feasibility was assessed via eligibility/baseline comparisons and overlap diagnostics. Endpoints at 24 weeks were MG-ADL response (≥3-point improvement) and QMG response (≥5-point improvement). For gefurulimab, the closest assessment was Week 26 to compare with Week 24 outcomes from RAISE. Effects were summarized as odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS: Base-case weighting achieved acceptable stability with effective sample size (ESS)=59 vs cemdisiran and ESS=66 vs gefurulimab; weight ranges were 0.14-3.42 and 0.21-2.47, respectively. In base-case analyses, zilucoplan showed statistically significant improvements in QMG response versus both comparators, while MG-ADL response was significant vs gefurulimab only. Versus cemdisiran, MG-ADL response OR was 2.01 (95% CI 0.70-5.73) and QMG response OR was 4.08 (95% CI 1.74-9.58). Versus gefurulimab, MG-ADL response OR was 3.92 (95% CI 1.62-9.48) and QMG response OR was 4.08 (95% CI 1.97-8.45). Sensitivity analyses were directionally consistent.
CONCLUSIONS: Zilucoplan demonstrated superior comparative efficacy versus gefurulimab for QMG and MG-ADL responses, and statistically significant improvements in QMG response versus cemdisiran. The studies had significant baseline differences and although efforts were made to adjust, residual confounding might remain. Whilst acknowledging uncertainty, these findings provide an indication of superior comparative efficacy of zilucoplan compared with cemdisiran, and gefurulimab.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO226
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Neurological Disorders, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)