Comparative analysis of the pivotal studies of extended half‐life recombinant FVIII products for treatment of haemophilia A

Abstract

The need to reduce the burden of injections, and improve adherence and clinical outcomes in haemophilia A led to the development of recombinant FVIII products endowed with an extended plasma half‐life (EHL‐rFVIII) in comparison with standard half‐life products (SHL‐rFVIII). Lack of head‐to‐head studies makes difficult to grasp the relative value of each treatment option. We conducted a combined evaluation of the individual pivotal trials in order to assess between‐product differences regarding the reported efficacy results and FVIII consumption. We evaluated 4 EHL‐rFVIII products available to treat patients with haemophilia A without inhibitors and also a SHL‐rFVIII as a comparator. In the frame of these clinical studies, all the EHL‐rFVIII products showed a decrease in the injection burden coupled with good clinical efficacy, even though there were between‐product differences in terms of reduction in injection frequencies. Further, between‐product differences in terms of weekly/yearly consumption of rFVIII expressed in IU/Kg were identified, suggesting a different economic impact for the different EHL‐rFVIII products in the context of comparable clinical efficacy. The present findings based upon the review of pivotal studies done in the frame of a highly selected clinical scenario should be integrated with real‐life data.

Matching-Adjusted Indirect Comparison of Efficacy and Consumption of rVIII-SingleChain Versus Two Recombinant FVIII Products Used for Prophylactic Treatment of Adults/Adolescents with Severe Haemophilia A

“…All estimates on ABR, percentages of patients with zero bleeds and rFVIII consumption were obtained through MAIC, which, in the absence of head-to-head RCT (the gold standard for comparative evidence generation), still provides a clear advantage over naïve comparisons [23,24]. For example, a recent naïve comparison by Mannucci and colleagues stated that it is impossible to draw conclusions on the superiority of one product versus another using this approach; additionally, different prophylaxis regimens or patient selection can also make comparisons challenging [32]. By using individual patient-level data from the adolescent/ adult patient population of the rVIII-Sin-gleChain phase I/III trial, MAIC corrected for Fig.…”

Illustrative Cases from the Pathfinder Clinical Trials of Patients with Hemophilia A Treated with Turoctocog Alfa Pegol (N8-GP)

“…The cases presented here illustrate some of the challenges associated with the treatment of severe hemophilia A and the potential ability of EHL products, such as N8-GP, to address these issues. 15 , 20 , 21 The strength of our case series is that all on-trial data were collected systematically as part of the pathfinder program. However, as for all case series, our study is limited by selection bias and potentially recall bias for subjective outcomes.…”

The Arrival of Gene Therapy for Patients with Hemophilia A

“…Currently, intravenous administration of exogenous FVIII, either as prophylaxis or episodically to treat bleeding events, trauma, or surgical procedures, constitutes the gold standard in hemophilia A treatment [ 2 , 13 , 14 , 15 ]. However, exogenous coagulation factors represent a significant burden to patients, impacting their health-related QoL.…”