Indirect treatment comparisons of the gene therapy etranacogene dezaparvovec versus extended half-life factor IX therapies for severe or moderately severe haemophilia B

Introduction: Etranacogene dezaparvovec gene therapy for haemophilia B demonstrated superior efficacy at 24 months in reducing bleeds versus a ≥6-month lead-in period of prophylaxis with FIX products in the phase 3 trial, HOPE-B. In the absence of head-to-head comparisons of etranacogene dezaparvovec versus FIX products, indirect treatment comparisons (ITC) can be used. Aim: To compare the efficacy of etranacogene dezaparvovec versus rIX-FP, rFIXFc and N9-GP using ITC, and support HOPE-B results. Methods: Data were leveraged from Phase 3 pivotal trials: HOPE-B, PROLONG-9FP, B-LONG and Paradigm 2. Annualised bleeding rates (ABR), spontaneous (AsBR) and joint (AjBR) bleeding rates, percentage of patients with no bleeds, and FIX consumption were assessed using inverse probability of treatment weighting and matching adjusted indirect comparisons. Results: Etranacogene dezaparvovec demonstrated statistically significantly lower bleeding rates versus all comparators. Rate ratios for ABR, AsBR and AjBR versus rIX-FP were 0.19 (p <.0001), 0.08 (p <.0001) and 0.09 (p <.0001), respectively. Rate ratios for ABR, AsBR and AjBR versus rFIXFc were 0.14 (p <.0001), 0.13 (p =.0083) and 0.15 (p =.0111), respectively. Rate ratios for ABR and AsBR, versus N9-GP were 0.24 (p =.0231) and 0.13 (p =.0071), respectively. Etranacogene dezaparvovec demonstrated significantly higher percentage of patients with no bleeds versus rIX-FP and rFIXFc; odds ratios: 17.60 (p <.0001) and 5.65 (p =.0037), respectively. Etranacogene dezaparvovec resulted in significantly lower FIX consumption than all comparators. Conclusions: ITC suggests that etranacogene dezaparvovec offers patients with haemophilia B (≤2% of normal FIX expression) a single dose treatment that can significantly reduce bleeding rates and eliminate routine infusions associated with FIX therapies.