A matching‐adjusted indirect comparison in patients with severe haemophilia A: Comparing the efficacy and consumption of rVIII-SingleChain vs two recombinant FVIII

Objective Head‐to‐head comparisons of recombinant factor VIII (FVIII) products in randomised controlled clinical trials are difficult to conduct due to the rarity of haemophilia. The objective of this matching‐adjusted indirect comparison was to compare the prophylactic efficacy and factor consumption of rVIII-SingleChain (lonoctocog alfa, AFSTYLA) versus rAHF-PFM (octocog alfa, Advate) and rFVIIIFc (efmoroctocog alfa, Elocta), for the treatment of bleeding episodes in previously treated adults/adolescents with severe haemophilia A.

Material and Methods Published clinical trials of rAHF‐PFM and rFVIIIFc in the target population were identified from a systematic literature search. Individual patient data from the rVIII-SingleChain pivotal study were used to match baseline patient characteristics to those from published trials, using an approach similar to propensity score weighting. After matching, treatment outcomes were compared across trial populations. For prophylaxis, annualised bleeding rates (ABR), percentage of patients with zero bleeds, and weekly FVIII consumption were analysed. Relative treatment effects are presented as risk ratios (RR), odds ratios (OR) and median differences (MD) with 95% confidence intervals.

Results For rVIII-SingleChain, the adult/adolescent patient population receiving prophylaxis in the phase I/III trial was selected (n=145). Three published clinical trials were identified: two for rAHF‐PFM (from 2004 [n=111] and 2012 [n=32]) and one for rFVIIIFc (from 2014, [n=118]). After matching, rVIII‐SingleChain had similar ABR (RR: 0.74 [0.16; 3.48]; RR: 1.18 [0.85; 1.65]) and percentage of patients with zero bleeds (OR: 1.34 [0.56; 3.22]; OR: 0.78 [0.47; 1.31]) vs rAHF‐PFM-2004 and rFVIIIFc, respectively. Median annualised rVIII‐SingleChain consumption was significantly lower than rAHF‐PFM (MD: −1507.66 IU/kg/year [−2011.71; −1003.61]) and equivalent to rFVIIIFc (RR: 0.96 [0.62; 1.49]).

Conclusion This study suggests that routine prophylaxis with rVIII-SingleChain in the conditions observed in the study results in consumption comparable to rFVIIIFc and significantly lower than rAHF-PFM, while maintaining a similar ABR and percentage of patients with zero bleeds, attesting to the long-acting nature of rVIII-SingleChain.

Publication History

Article published online:
18 June 2021