Paroxysmal nocturnal hemoglobinuria (PNH) is a debilitating and potentially deadly blood disorder that has seen advancements in treatment options with the recent approval of two Soliris biosimilars by the US Food and Drug Administration (FDA). These approvals mark significant progress in the treatment landscape for PNH and atypical hemolytic uremic syndrome, another rare condition.
The first biosimilar, Bkemv (eculizumab-aeeb, Amgen), received FDA approval in May, while the second, Epysqli (eculizumab-aagh, Samsung Bioepis), was approved more recently. Both biosimilars are monoclonal antibodies designed to bind to complement protein C5, mirroring the mechanism of Soliris (eculizumab, Alexion), which has been a critical treatment for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome, as well as for generalized myasthenia gravis and neuromyelitis optical spectrum disorder.
Paroxysmal Nocturnal Hemoglobinuria: FDA Approval of Bkemv Delayed Until March 2025 Due to Patent Settlement
Bkemv’s availability in the United States is delayed until March 1, 2025, due to a patent settlement agreement between Alexion and Amgen. The FDA’s approval of Bkemv was based on the double-blind, active-controlled, phase 3 DAHLIA study. This study demonstrated comparable efficacy, safety, and immunogenicity to Soliris in adults with PNH. Specifically, Bkemv was shown to reduce the loss of red blood cells and decrease the need for blood transfusions in paroxysmal nocturnal hemoglobinuria patients.
The DAHLIA study included 42 adults with PNH who had been on Soliris for at least six months. These participants were randomized to receive either Soliris or Bkemv in one of two sequences over two treatment periods. In the first study period (weeks 1-53), patients received 900 mg of intravenous (IV) Bkemv or Soliris every 14 days for 52 weeks. In the second study period, patients crossed over to the alternative treatment for 26 weeks.
Paroxysmal Nocturnal Hemoglobinuria: Comparable Efficacy of Bkemv and Soliris Observed in Phase 3 DAHLIA Study
Comparable efficacy was observed in both parallel and crossover comparisons, with similar geometric mean values for trough total and unbound concentrations of Bkemv and Soliris at all tested time points. Control of intravascular hemolysis was assessed by lactate dehydrogenase levels at week 27 for the parallel comparison and by the time-adjusted area under the effect curve of lactate dehydrogenase from weeks 13 to 27, weeks 39 to 53, and weeks 65 to 79 for the crossover comparison.
Epysqli’s approval was based on findings from a phase 3 trial involving 50 patients with paroxysmal nocturnal hemoglobinuria. Participants were randomized to receive either Epysqli or Soliris through week 26, after which treatments were switched and provided until week 50. Results indicated a mean difference in lactate dehydrogenase levels at week 26 between Epysqli and Soliris was 34.48 U/L, which fell within the predefined equivalence margin. The ratio of time-adjusted area under the effect curve of lactate dehydrogenase between the two treatments was 1.08, also within the predefined equivalence margin, indicating bioequivalence between Epysqli and Soliris.
Similar to Soliris, the prescribing information for both Bkemv and Epysqli includes a boxed warning about the increased risk of serious meningococcal infections. Due to this risk, both biosimilars are available only under a Risk Evaluation and Mitigation Strategy (REMS) program, which requires prescribers to enroll and adhere to specific safety protocols.
These biosimilars offer promising alternatives for patients with PNH, providing similar therapeutic benefits as Soliris. The availability of these treatments under managed care programs will potentially improve access and reduce the economic burden on the healthcare system while ensuring patient safety through stringent monitoring and risk management strategies. As the landscape of paroxysmal nocturnal hemoglobinuria treatment continues to evolve, these advancements signify hope for better management of this challenging condition, ultimately aiming to enhance the quality of life for those affected by paroxysmal nocturnal hemoglobinuria and related disorders.
Resource: Med Scape, July 24, 2024
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