Editor's Note: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and life-threatening blood disorder. Due to the complexity of complement biology and various pathogenic pathways, there remains a significant unmet clinical need, urgently requiring next-generation drugs with superior efficacy and dosing convenience compared to current therapies. At the recently held 65th American Society of Hematology (ASH) Annual Meeting, Prof. Fengkui Zhang from the Hematology Hospital of the Chinese Academy of Medical Sciences (Institute of Hematology) and Prof. Bing Han's team from Peking Union Medical College Hospital presented an oral report (Abstract: 572). The study explored the safety and effectiveness of the dual-function C5 antibody/H factor fusion protein KP104 in PNH patients who had not received complement inhibitor treatment. This research brings hope to address this challenging issue and has been selected as a highlight of "ASH 2024." The summarized details are presented below in this issue of "Hematology Insight."
The researchers stated:
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and life-threatening blood disorder caused by the overactivity of the complement system, which belongs to the innate immune system. PNH is characterized by red blood cell destruction, thrombosis, and impaired bone marrow function, affecting 1 to 5 individuals per million. Due to the complexity of complement biology and various pathogenic pathways in PNH, there remains a significant unmet clinical need for next-generation drugs with better efficacy and dosing convenience compared to current therapies. Current treatments include C5 inhibitors, which fail to address extravascular hemolysis (EVH) associated with alternative pathways, or C3 inhibitors, which may resolve EVH but face challenges in fully blocking downstream C5, leading to life-threatening breakthrough hemolysis.
KP104, developed by the SciClone Pharmaceuticals team led by Professor Wenru Song, is a globally pioneering dual-function complement biologic with a unique mechanism of action. It can selectively inhibit both the complement alternative pathway and terminal pathway, offering a powerful synergistic mechanism and potentially more selective precision in treating complement-mediated diseases. In our Phase II study presented at the ASH conference for PNH patients who had not received complement inhibitor treatment, positive results were observed. Eighteen patients completed 24/25 weeks of treatment, and mid-term analysis indicated that KP104 is safe, well-tolerated, and successfully met all major and secondary endpoints. KP104 effectively controlled intravascular and extravascular hemolysis, with all 18 patients experiencing an increase in hemoglobin by ≥2 g/dL compared to baseline without requiring transfusions. Moreover, most patients achieved normal ranges of hemoglobin and LDH levels. The mid-term results support advancing KP104 to Phase III clinical trials as a potentially optimal and safe treatment for PNH patients, addressing the current unmet clinical needs. Notably, this oral presentation on KP104 not only made it to the “ASH Highlights 2024” but also received recognition at the ASH President’s Symposium, securing the top position on the “2023 Novel PNH Inhibitors List.”
Professor Fengkui Zhang:
– Degrees: Ph.D.
– Professional Titles: Chief Physician, Professor, Doctoral Supervisor
– Affiliation: Hematology Hospital, Chinese Academy of Medical Sciences (Institute of Hematology)
– Leadership Roles:
– Director of the Anemia Diagnosis and Treatment Center, Hematology Hospital, Chinese Academy of Medical Sciences (Institute of Hematology)
– Director of the National New Drug Clinical Trial Institution, Hematology Hospital, Chinese Academy of Medical Sciences (Institute of Hematology)
– **Research Focus:** Clinical and experimental research on hematopoietic system red blood cell diseases
– **Pioneering Contributions:**
– Pioneered systematic reports on Large Granular Lymphocyte Leukemia in China
– Investigated and reported on congenital red blood cell disorders causing abnormal erythropoiesis
– Explored genetic instability in hematopoietic cells in patients with bone marrow failure
– Led the use of ATG combined with CsA and high-dose cyclophosphamide as a first-line treatment for bone marrow failure
– Editorial Roles:
– Deputy Editor-in-Chief of the “Chinese Journal of Hematology”
– Editorial board member of various hematology specialized journals
– Research Contributions:
– Principal investigator and participant in numerous research projects
– Published over ninety research papers
– Awards and Recognitions:
– Recipient of several awards, including recognition as an outstanding worker, excellent Communist Party member, outstanding teacher at the Medical Academy, and the “May 1st Labor Medal” in Tianjin
Professor Zhang’s extensive expertise, leadership, and contributions to the field of hematology underscore his commitment to advancing knowledge and improving the diagnosis and treatment of hematologic disorders.
Professor Bing Han:
– Degrees: Ph.D.
– Professional Titles: Chief Physician, Professor, Doctoral Supervisor
– Affiliation: Chief of the Hematology Department, Peking Union Medical College Hospital
– Leadership Roles:
– Leader of the Red Blood Cell Disease Group, Hematology Department, Peking Union Medical College Hospital
– Core Member of the International PNH Interest Group (IPIG)
– Deputy Director of the Red Blood Cell Disease Group, Chinese Medical Association Hematology Branch
– Head of the PNH Group, Chinese Medical Association Hematology Branch Rare Disease Group
– Deputy Director of the Academic Working Committee on Red Blood Cell Diseases, Second Committee of the Hematology Branch of the Chinese Medical Association Geriatrics Society
– Deputy Group Leader of the Second Committee of the MDS and MPN Working Group, Chinese Anti-Cancer Association Hematology Oncology Professional Committee
– Deputy Group Leader of the MDS Disease Group, Chinese Women Doctors Association
– Deputy Director of the Red Blood Cell Committee, Beijing Cancer Prevention and Treatment Society
– Deputy Director of the Cytology Professional Committee, Bai Qiu’en Spirit Research Association Laboratory Medicine Branch
– Deputy Director of the Red Blood Cell Disease Diagnosis Committee, Chinese Medical Doctor Association Laboratory Medicine Branch
– Standing Committee Member, Chinese Medical Association Geriatrics Hematology Branch
– Executive Director, World Federation of Chinese Medicine Societies
– Committee Member, Beijing Rare Disease Society
Professor Han’s diverse leadership roles across various medical associations and committees highlight her significant contributions to hematology research, rare disease advocacy, and medical professional organizations.
