Pegcetacoplan 1.08g/20ml solution for infusion vials

PurposeTo evaluate the impact of pegcetacoplan on its ability to slow the loss of visual function using microperimetry endpoints in eyes with geographic atrophy secondary to age-related macular degeneration (AMD).DesignPost hoc analysis of phase 3 randomized controlled trial data.MethodsUtilizing data from the OAKS study, which evaluated pegcetacoplan monthly (PM) or every other month (PEOM) vs sham for the treatment of GA secondary to AMD, microperimetry endpoints were assessed at baseline and every 6 months until 24 months, using a 10-2 grid composed of 68 points with a 4-2 threshold strategy. Main outcome measures included the time to development of absolute scotomas in the 4 and 16 central macular points. The number of absolute scotomatous points and mean retinal sensitivity (dB) within the junctional zone extending to 250 µm on either side of autofluorescence-determined GA border was analyzed for change from baseline.ResultsAmong 605 patients with subfoveal or nonsubfoveal GA, treatment with pegcetacoplan delayed time to development of absolute scotomas of all 4 central macular points compared to sham at 24 months (PM: hazard ratio [HR]: 0.66 [34% risk reduction]; 95% confidence interval [CI]: 0.46, 0.96; P = .0282; PEOM: HR: 0.64 [36% risk reduction]; 95% CI: 0.44, 0.92; P = .0164). Similarly, PM and PEOM treatment delayed time to development of absolute scotomas of all 16 central points (PM: HR: 0.57 [43% risk reduction]; 95% CI: 0.33, 0.96; P = .0361; PEOM: HR: 0.52 [48% risk reduction]; 95% CI: 0.32, 0.85; P = .0084). Across the junctional zone of GA, pegcetacoplan-treated eyes developed fewer absolute scotomatous points (PM difference vs sham pooled: -0.68 points, P = .1444; PEOM difference vs sham pooled: -1.14 points, P = .0140) and experienced decreased loss of mean retinal sensitivity (PM difference vs sham pooled: 0.56 dB, P = .0650; PEOM difference vs sham pooled: 0.71 dB, P = .0202) compared with sham at 24 months.ConclusionsMicroperimetry demonstrates a reduced rate of visual function loss in the central macula and junctional zone with pegcetacoplan treatment in GA due to AMD.

Abstract licence: CC BY-NC-ND

Aim: To map patient-level data collected on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 to EQ-5D-5L data for estimating health-state utilities in patients with paroxysmal nocturnal hemoglobinuria (PNH). Materials & methods: European cross-sectional PNH patient survey data populated regression models mapping EORTC QLQ-C30 domains (covariates: sex and baseline age) to utilities calculated with the EQ-5D-5L French value set. A genetic algorithm allowed selection of the best-fitting between a set of models with and without interaction terms. We validated the selected algorithm using EQ-5D-5L utilities converted from EORTC QLQ-C30 data collected in the PEGASUS phase III, randomized controlled trial of pegcetacoplan versus eculizumab in adults with PNH. Results: Selected through the genetic algorithm, the ordinary least squares model without interactions provided highly stable results across study visits (mean [±SD] utilities 0.58 [±0.42] to 0.89 [±0.10]), and showed the best predictive validity. Conclusion: The new PNH EQ-5D-5L direct mapping developed using a genetic algorithm enabled calculation of reliable health-state utility data required for cost–utility analysis in health technology assessments supporting treatments of PNH.

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IntroductionC3 glomerulopathy (C3G) is a rare complement-mediated kidney disease. Pegcetacoplan [targeted complement 3 (C3)/C3b inhibitor] and iptacopan (factor B inhibitor) target the complement system and are approved for treatment of C3G in adults and adolescents (pegcetacoplan) or adults only (iptacopan). Currently, no head-to-head randomized controlled trials (RCTs) have assessed their relative efficacy.MethodsIndirect treatment comparisons (ITCs) were conducted using the Bucher (primary analysis-preserves randomization) and matching-adjusted indirect comparison (MAIC; supportive analyses-adjusts for trial differences) methodologies and data from two similarly designed, placebo-controlled, Phase III RCTs in C3G/primary immune-complex membranoproliferative glomerulonephritis [VALIANT (NCT05067127)] and C3G only [APPEAR-C3G (NCT04817618)]. Relative efficacy was assessed at 6 months (anchored Bucher and MAIC) and 12 months (anchored Bucher/MAIC plus unanchored MAIC).ResultsAt 6 months, the Bucher analysis demonstrated pegcetacoplan was associated with a significantly greater reduction in urine protein-creatinine ratio (UPCR) relative to baseline versus iptacopan [mean difference -50.90% (95% confidence interval: - 67.34, - 26.18); p ConclusionThese ITCs indicate that, in patients with C3G, pegcetacoplan is associated with greater reductions in proteinuria levels, and more patients achieved the composite renal endpoint compared with iptacopan. The relative efficacy benefits for pegcetacoplan observed at 6 months were sustained at 12 months. These comparative effectiveness findings may help clinicians and payers better understand the utility of new therapies to treat patients with C3G.

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