Long-term therapy with eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria: Two-year interim results of a prospective multicenter observational study

Abstract Introduction: The complement C5-inhibition with eculizumab or ravulizumab is a current standard of care in patients with paroxysmal nocturnal hemoglobinuria (PNH). Elizaria® is the first registered biosimilar of eculizumab. The prospective multicenter observational study ECU-PNH-N02 was initiated to evaluate the results of long-term therapy with a biosimilar of eculizumab (Elizaria®) in a Russian cohort of patients with PNH in accordance with national treatment protocols. Methods: The two-year interim results included 265 patients with a confirmed diagnosis of PNH, prescribed eculizumab and an informed consent form signed by the patient and their legal representative (for a minor patient). Eculizumab-naive patients with baseline LDH level ≥1.5 times the upper limit of normal started induction phase of four weekly infusion of the study medications at dose of 600 mg, with subsequent maintenance therapy at dose of 900 mg every two weeks. Previously treated patients started the study treatment at the maintenance dose. Interim analysis included four visits and the total treatment duration for each patient was nearly 48 weeks. The main efficacy parameters were LDH and hemoglobin levels dynamics, response to treatment with eculizumab, breakthrough hemolysis, extravascular hemolysis and transfusion dependence. Quality of life was assessed during the treatment using the FACIT-F and FACIT-F peds scales. Results: The interim analysis included 265 patients aged 42±15 years, male/female – 40/60%, Caucasians -94% and Asians - 6%. The LDH level decreased from 414 U/l on visit 1 to 327.5 U/l on visit 4 (p<0.007). The average hemoglobin level was 106 g/l on screening and 109 g/l on visit 4. Proportion of patients in the general group with a complete, major, or good response to targeted therapy were 20.5%, 0.8%, 45.8%, respectively. In male patients, the proportion of optimal response was higher and amounted to 78.2% on visit 4. The proportion of patients requiring blood transfusion decreased from 22% at screening to 12% at visit 4 (p < 0.001). The proportion of patients with breakthrough hemolysis tended to decrease from 8% at screening to 3% at visit 4 (p = 0.08). The proportion of patients with clinically significant extravascular hemolysis was lower at visit 4 10% compared to screening 18% (p < 0.001). The safety profile of eculizumab biosimilar was characterized by 15 adverse reactions in 10 (3.8%) patients in the study, of which 12 were mild, two were moderate, and one was severe (pneumonia). The quality of life level was 35.9±9.1 points during screening and 37±9.8 points at the end of analyzed period. Conclusion: Thus, the results of the study indicate a long-term stable course of PNH during safe and effective treatment with a biosimilar of eculizumab. Acknowledgments: The authors thank all the investigators and patients who participated and continues to participate in this study.