Introduction: Given the relatively small number of patients with haemophilia A, head-to-head comparisons between recombinant FVIII (rFVIII) products are difficult to conduct. This study compared the efficacy and consumption of rVIII-SingleChain (lonoctocog alfa, AFSTYLA®) with rAHF-PFM (octocog alfa, Advate®) and rFVIIIFc (efmoroctocog alfa, Elocta®), for the prophylaxis and treatment of bleeding episodes in previously treated adolescents/adults with severe haemophilia A, through a matching-adjusted indirect comparison (MAIC).
Methods: A systematic literature review identified published clinical trials for rAHF-PFM and rFVIIIFc. Individual patient data for rVIII-SingleChain were used to match baseline patient characteristics to those from published trials, using an approach similar to propensity score weighting. After matching, annualized bleeding rates (ABR), percentage of patients with zero bleeds, and rFVIII consumption were compared across trial populations.
Results: Published data were identified from two rAHF-PFM trials and one rFVIIIFc trial. rVIII-SingleChain had similar ABR (risk ratio [RR]: 0.74 [0.16; 3.48]; RR: 1.18 [0.85; 1.65]) and percentage of patients with zero bleeds (odds ratio [OR]: 1.34 [0.56; 3.22]; OR: 0.78 [0.47; 1.31]) versus rAHF-PFM and rFVIIIFc, respectively. Annual rVIII-SingleChain consumption was significantly lower than rAHF-PFM (mean difference: - 1507.66 IU/kg/year [- 2011.71; - 1003.61]) and equivalent to rFVIIIFc (RR: 0.96 [0.62; 1.49]).
Conclusion: Although limited to published information for comparator trials, these results suggest that with an annualized rFVIII consumption comparable to rFVIIIFc, but significantly lower than rAHF-PFM, routine prophylaxis with rVIII-SingleChain is able to maintain a similar ABR and percentage of patients with zero bleeds, attesting to the long-acting nature of rVIII-SingleChain.
Keywords: Annualized bleeding rate; Efmoroctocog alfa; FVIII consumption; Haemophilia A; Lonoctocog alfa; MAIC; Matching-adjusted indirect comparison; Octocog alfa; rVIII-SingleChain.
It is difficult to directly compare different recombinant FVIII products in head-to-head studies because there are few patients with haemophilia A. This study aimed to indirectly compare the efficacy and consumption of different recombinant FVIII products in the prophylactic treatment of haemophilia A using published clinical data. A proven method for performing indirect comparisons of products is referred to as a matching-adjusted indirect comparison. Using this approach, we were able to compare rVIII-SingleChain with two other recombinant FVIII products (rAHF-PFM and rFVIIIFc). Our results suggest that annual FVIII consumption with rVIII-SingleChain is comparable to rFVIIIFc, but is significantly lower than rAHF-PFM, while maintaining a similar bleeding rate. These results highlight the long-acting nature of the product.
© 2021. The Author(s).