Complement C5 inhibitors have transformed the management of paroxysmal nocturnal hemoglobinuria (PNH) and remain the current standard first-line therapy. However, despite effective control of intravascular hemolysis, many patients continue to experience persistent anemia, limited hemoglobin recovery, and clinically significant extravascular hemolysis, leaving substantial unmet medical needs.At the 2026 European Hematology Association (EHA) Congress, Professor Fengkui Zhang of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, presented findings demonstrating that the oral complement Factor B inhibitor MY008211A achieved superior outcomes compared with eculizumab in complement inhibitor-naïve Chinese patients with PNH.
In an interview with Oncology Frontier – Hematology Frontier, Professor Zhang discussed the clinical significance of these findings and the potential impact of Factor B inhibition on the future treatment landscape of PNH.
Addressing Unmet Needs Beyond C5 Inhibition
Oncology Frontier – Hematology Frontier:
Although C5 inhibitors have become the standard treatment for PNH, many patients continue to experience persistent anemia and inadequate hemoglobin recovery. This study showed that MY008211A significantly outperformed eculizumab in transfusion independence and hemoglobin normalization. What impact could these findings have on treatment goals and clinical practice?
Professor Fengkui Zhang:
Eculizumab, the first approved complement inhibitor, ushered in a new era of modern PNH treatment. However, as a downstream complement inhibitor, it has an inherent limitation. While it effectively suppresses intravascular hemolysis and stabilizes hemoglobin levels, it may also contribute to clinically relevant extravascular hemolysis.
For this reason, the development of upstream complement inhibitors has become a major focus in PNH research.
MY008211A is a Factor B inhibitor, belonging to the same therapeutic class as iptacopan. By targeting complement activation upstream, Factor B inhibition can control intravascular hemolysis while simultaneously preventing the development of extravascular hemolysis. As a result, patients may achieve significantly higher hemoglobin levels and lower reticulocyte counts.
Another major advantage is convenience. Unlike downstream complement inhibitors that require intravenous administration, MY008211A is an oral therapy. This provides greater treatment flexibility and convenience, potentially improving long-term adherence while delivering meaningful clinical benefits.
Why Factor B Inhibition Matters
Oncology Frontier – Hematology Frontier:
The study demonstrated not only superior hemolysis control but also greater improvements in hemoglobin and reductions in reticulocyte counts. What are the key mechanistic advantages of Factor B inhibition compared with traditional C5 inhibition, and what might these advantages mean for long-term outcomes?
Professor Fengkui Zhang:
The differences become particularly evident when examining clinical efficacy data.
At weeks 18 to 24, approximately 50% of patients receiving MY008211A achieved normal hemoglobin levels (Hb ≥120 g/L), compared with only 9.1% of patients treated with eculizumab. This represents a substantial and clinically meaningful difference.
From a pharmacodynamic perspective, MY008211A demonstrated clear superiority. Beyond efficacy, the oral formulation provides patients with a level of independence that intravenous therapies cannot offer. Patients can manage their treatment at home without the burden of frequent hospital visits and infusion appointments.
Importantly, the significant improvement in hemoglobin levels translates directly into better quality of life. Improved energy levels, reduced symptoms of anemia, and enhanced daily functioning all contribute to stronger treatment adherence and better long-term disease management.
In many ways, this reflects the evolution of PNH care—from an era when no effective therapies existed, through a period of partial disease control, to a new phase in which patients may achieve both meaningful hematologic recovery and highly convenient chronic disease management.
Potential Future Role of MY008211A
Oncology Frontier – Hematology Frontier:
As an oral complement inhibitor, MY008211A offers both efficacy and convenience. Based on the current data, how do you envision its future role in PNH treatment? Which patients are most likely to benefit?
Professor Fengkui Zhang:
Simply put, virtually all patients with PNH may benefit from treatment with MY008211A.
This includes patients who have previously received downstream complement inhibitors and subsequently transition to MY008211A, as well as treatment-naïve patients who have never received complement inhibition.
The data suggest that both groups can derive substantial clinical benefit.
As the treatment landscape continues to evolve, Factor B inhibitors have the potential to become a preferred first-line option for patients with hemolytic PNH. By addressing both intravascular and extravascular hemolysis while offering the convenience of oral administration, these agents may provide a more comprehensive therapeutic approach and ultimately improve patient outcomes.
Looking Ahead
The emergence of Factor B inhibition represents an important shift in the treatment paradigm for PNH. Rather than focusing solely on controlling intravascular hemolysis, newer upstream complement inhibitors aim to deliver deeper hematologic responses, better hemoglobin recovery, and improved quality of life.
The results presented at EHA 2026 suggest that MY008211A may help close longstanding treatment gaps associated with C5 inhibition and potentially redefine expectations for first-line therapy.
If future studies continue to confirm these findings, oral Factor B inhibitors could play a central role in the next generation of PNH management, moving the field closer to achieving complete disease control while minimizing treatment burden.
Expert Profile
Professor Fengkui Zhang
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Chief Clinical Expert, Professor, MD, PhD Supervisor
Professor Zhang specializes in the clinical and translational research of red blood cell disorders and hematologic diseases.
He was among the first investigators to systematically report several important hematologic conditions and treatment strategies in China, including large granular lymphocytic leukemia, congenital dyserythropoietic anemia, genomic instability in aplastic anemia, and frontline use of antithymocyte globulin (ATG) combined with cyclosporine or high-dose cyclophosphamide for aplastic anemia.
Professor Zhang serves as Deputy Editor-in-Chief of the Chinese Journal of Hematology and sits on the editorial boards of multiple hematology journals. He has authored more than 90 scientific publications and has received numerous honors for his contributions to clinical medicine, medical education, and hematology research.
