From December 7 to 10, 2024, the 66th American Society of Hematology (ASH) Annual Meeting took place in San Diego, USA, where leading experts in hematology gathered to discuss the latest research advancements.
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and life-threatening hematologic disorder characterized by intravascular hemolysis (IVH) and extravascular hemolysis (EVH). The complex and evolving pathophysiology of PNH makes clinical management particularly challenging. At ASH 2024, new findings were presented on KP104, a first-in-class bifunctional complement inhibitor (C5 Antibody/Factor H Fusion Protein), highlighting its therapeutic potential in PNH (Abstract P2699).
To provide deeper insights into these findings, Hematology Frontier invited Dr. Fengkui Zhang from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Dr. Bing Han from Peking Union Medical College Hospital to discuss the study’s clinical significance and the latest advancements in PNH treatment.
Dr. Fengkui Zhang: PNH is a rare and life-threatening hematologic disease, driven by abnormal hyperactivation of the innate immune complement system, leading to accelerated red blood cell destruction, increased thrombotic risk, and bone marrow dysfunction.
He added, “Given the complexity of complement biology and the diverse pathological mechanisms of PNH, current treatment options remain limited in improving hemoglobin levels. Some patients continue to face challenges such as intravascular hemolysis (IVH) or breakthrough hemolysis (BTH) despite existing therapies. This underscores the urgent need for novel therapies with superior efficacy and more convenient administration. The latest long-term clinical results of KP104 demonstrate its best-in-class potential in PNH treatment.”
Dr. Bing Han: Professor Han agreed with this perspective and elaborated further, stating, “KP104, as a first-in-class bifunctional complement-targeting therapy, simultaneously inhibits both the alternative and terminal complement pathways, resulting in an extended half-life and enhanced pharmacodynamic effects. In PNH patients, KP104 not only effectively alleviates hemolysis but also significantly improves hemoglobin levels, allowing many patients to become transfusion-independent.”
She continued, “The updated study data presented at ASH further confirm KP104’s ability to provide a sustained increase in hemoglobin levels and improve overall hematologic parameters. This offers a promising new treatment option for patients who are either complement therapy-naïve or have shown inadequate response to existing complement inhibitors.”
Looking ahead, both professors expressed optimism: “We eagerly anticipate the successful progress of global Phase III clinical trials, as KP104 has the potential to become the preferred first-line therapy for PNH. Its widespread application will not only provide a new standard of care but also expand treatment options for PNH patients worldwide.”
Dr. Fengkui Zhang
Institution: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences Title: MD, Chief Physician, Professor, Doctoral Supervisor Clinical Lead: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences Research Focus: Clinical and experimental studies on red blood cell disorders in the hematopoietic system Achievements:
- First to systematically report large granular lymphocytic leukemia (LGL leukemia), congenital dyserythropoietic anemia, and hematopoietic cell genetic instability in aplastic anemia (AA) in China
- Pioneered ATG combined with CsA and high-dose cyclophosphamide as first-line treatments for AA
- Deputy Editor-in-Chief of Chinese Journal of Hematology and editorial board member of multiple hematology journals
- Principal investigator in multiple research projects and author of over 90 publications
- Recipient of numerous awards, including Outstanding Communist Party Member, Distinguished Teacher at the Academy of Medical Sciences, and Tianjin May Day Labor Medal
Dr. Bing Han
Institution: Department of Hematology, Peking Union Medical College Hospital Title: Chief Physician, Doctoral Supervisor Leadership Roles:
- Head of the Red Blood Cell Disorders Group, Department of Hematology, Peking Union Medical College Hospital
- Core Member of the International PNH Interest Group (IPIG)
- Vice Chair of the Red Blood Cell Disorders Group, Chinese Society of Hematology, Chinese Medical Association
- Chair of the PNH Subgroup, Rare Diseases Group, Chinese Society of Hematology, Chinese Medical Association
- Vice Chair of the Red Blood Cell Disorders Academic Committee, Geriatric Hematology Division, Chinese Society of Geriatrics
- Member of the Hematologic Oncology Committee, Chinese Anti-Cancer Association
- Vice Chair of the MDS and MPN Working Group, Second Committee, Chinese Society of Hematology
- Vice Chair of the MDS Disease Group, Chinese Women’s Medical Association
- Vice Chair of the Red Blood Cell Disorders Committee, Beijing Cancer Prevention and Treatment Society
- Vice Chair of the Cytomorphology Committee, Laboratory Medicine Branch, Bethune Spirit Research Association
- Vice Chair of the Red Blood Cell Disease Diagnostics Committee, Laboratory Medicine Branch, Chinese Medical Doctor Association
- Standing Member of the Geriatric Hematology Division, Chinese Medical Association
