Samsung Bioepis announced that its eculizumab biosimilar candidate successfully completed its phase 3 trial in patients with paroxysmal nocturnal hemoglobinuria (PNH). The randomized, double-blind, crossover trial pitted the eculizumab biosimilar against the reference biologic Soliris® in 50 patients.
Twenty-five patients received either SB12 or Soliris® 600 mg intravenously every week for 4 weeks, followed by 900 mg in week 5, and 900 mg every two weeks until week 26. Patients switched therapies at week 26 and continued until the 30th week of study.
Paroxysmal nocturnal hemoglobinuria is a disorder in which red blood cells made by defective bone marrow stem cells are destroyed prematurely by the body’s immunologic system, often resulting in anemia. It affects approximately 1 person per million in the general population.
The study results were announced at the 2022 meeting of the European Hematology Association in Vienna on June 10. The researchers studied the medication’s effect on patient’s lactate dehydrogenase (LDH) levels (a marker for intravascular hemolysis), pharmacokinetics and pharmacodynamics, and safety and immunogenicity compared with the reference product. At week 26, patients receiving the biosimilar SB12 had LDH levels that were within the prespecified equivalence margin. The same was true of other LDH measurements at weeks 14 to 26 and weeks 40 to the end of the follow-up. Treatment-emergent adverse events were reported in 72% of those assigned to SB12 and 68% of those taking Soliris. Mean serum trough concentrations of eculizumab were similar in each patient group. The researchers concluded that the biosimilar was clinically equivalent to the reference biologic and they were “comparable in terms of safety, pharmacokinetics, pharmacodynamics, and immunogenicity.”
The complement inhibitor eculizumab was approved in 2007 for the treatment of PNH, atypical hemolytic uremic syndrome (aHUS), and generalized myasthenia gravis (all considered rare conditions). Alexion’s Soliris will likely face eculizumab biosimilar competition no later than 2025 from either Samsung or Amgen. (Alexion is now part of AstraZeneca.) Amgen’s clinical study on its candidate ABP 959 is scheduled to conclude in July, but they signed an agreement with Alexion to delay launch to 2025. Despite its rare disease indications, Soliris brought $1.0 billion in 2021 US sales to Alexion. However, Alexion’s follow-on product Ultomiris® is gaining marketshare; it is administered every 8 weeks, instead of every other week. Its US sales were $380 million, growing at 20%.