Key points

We report findings from a phase 2 study of MY008211A among Chinese men and women aged ≥18 years with paroxysmal nocturnal hemoglobinuria

Increases in hemoglobin of ≥20 g/L were maintained for up to 44 weeks of treatment with MY008211A in all 34 patientsiv

Explanation of novelty Paroxysmal nocturnal hemoglobinuria is characterized by red blood cell (RBC) destruction and a prothrombotic state.v Treatments exist such as complement 5 inhibitors but these carry the risk for iatrogenic extravascular hemolysis and anemia.vi As reported here, the novel, oral complement factor B inhibitor MY008211A yielded increases in hemoglobin and RBC levels, while adverse events over 44 weeks were largely mild to moderate in severity, and infections generally consisted of respiratory infections.vii

Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease characterized by red blood cell (RBC) destruction, blood clots, and impaired bone marrow function.viii We evaluated the efficacy and safety of 3 dosages of MY008211A, a novel complement factor B inhibitor,ix for treating PNH.x This was a multicenter, open-label, phase 2, dose-finding study of MY008211A among Chinese men and women with complement inhibitor–naive PNH and signs of active hemolysis.xi Patients with hemoglobin <100 g/L were assigned to oral MY008211A 400 mg twice daily (BID), 600 mg BID, or 800 mg once daily (QD) for 12 weeks and could then continue treatment with 400 mg BID during a 32-week extension.xii The primary endpoint was the proportion of patients achieving an increase in hemoglobin concentration of ≥20 g/L vs baseline on day (D)84, without RBC transfusions after 4 weeks of dosing.xiii Safety assessments included adverse events (AEs).xiv Fifteen, 9, and 10 patients were assigned to MY008211A 400 mg BID, 600 mg BID, and 800 mg QD, respectively.xv All patients completed the study and its 32-week extension.xvi On D84, all 34 patients achieved increases in hemoglobin concentration of ≥20 g/L from baseline;xvii all patients maintained this increase at D308.xviii Through D308, grade ≥3 AEs occurred in 5 (33%), 5 (56%), and 4 (40%) patients in the 400-, 600-, and 800-mg groups, respectively.xix There were no deaths.xx In this multicenter, open-label study of 3 dosages of MY008211A for PNH, all patients achieved and maintained increases in hemoglobin of ≥20 g/L from baseline without RBC transfusions.

Y.C., R.X., C.T., L.L., X.G., Y.Z., X.L., R.K., W.C.W., and G.R., are employees of Createrna. F.Z., B. H., H.T. have received research grants from Createrna. C. X. is a scientific advisor of Createrna. C.D.C. declares relationships with Alexion, Apellis, Genentech, InnaRx, Novartis, Omeros, and Regeneron. All other authors declare no competing interests.

NCT06050226

This study was funded by Wuhan Createrna Science and Technology Co., Ltd.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences gave ethical approval for this work

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All data produced in the present study are available upon reasonable request to the authors