Keymed Biosciences has announced groundbreaking results for its BCMA x CD3 bispecific antibody CM336 in treating refractory autoimmune hemolytic anemia (AIHA), with findings published in the New England Journal of Medicine representing the first global report of BCMA-targeted therapy for this challenging indication.
Rapid Clinical Response in Treatment-Refractory Patients
The study, led by Prof. Jun Shi's research team from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, demonstrated remarkable efficacy in two patients with refractory AIHA. Both patients achieved partial remission within 13 and 19 days of CM336 administration, respectively, with hemoglobin levels returning to normal by days 17 and 21.
The clinical improvements were accompanied by significant decreases in key disease markers, including reticulocyte counts, lactate dehydrogenase, and indirect bilirubin levels. These patients had previously undergone extensive treatment regimens including glucocorticoids, splenectomy, anti-CD20 antibodies, BTK inhibitors, and CD19 CAR-T cell therapies, but their disease had recurred or progressed to refractory status.
Sustained Remission Without Ongoing Therapy
The most striking aspect of the results was the durability of response. After six months of follow-up, both patients remained in sustained remission without requiring immunosuppressive therapies or blood transfusions. This sustained response represents a significant clinical achievement for patients with treatment-refractory AIHA, a condition that typically requires ongoing immunosuppression.
Favorable Safety Profile
CM336 demonstrated an excellent safety profile throughout the treatment and follow-up period. Notably, no patients experienced cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or infection events. This safety profile is particularly significant given the immunocompromised state of patients with refractory AIHA and their history of multiple prior therapies.
Mechanism of Action and Development Pipeline
CM336 functions as a BCMA x CD3 bispecific antibody that simultaneously binds BCMA on target cells and CD3 receptors on T cells, recruiting immune T cells to eliminate target cells through T-cell dependent cellular cytotoxicity (TDCC). This mechanism represents a novel approach to treating autoimmune conditions by targeting BCMA-expressing cells.
The success in AIHA has broader implications for CM336's development program. The Center for Drug Evaluation of the National Medical Products Administration has approved a Phase II clinical study of CM336 for treating primary light-chain amyloidosis, which will commence shortly.
Clinical Significance for Refractory Disease
The study results position CM336 as a potentially innovative treatment option for patients with relapsed/refractory AIHA who have exhausted conventional therapies. The rapid disease control and sustained remission lasting over six months, combined with the favorable safety profile, address a significant unmet medical need in this patient population.
For patients who have failed multiple lines of therapy including advanced treatments like CAR-T cell therapy, CM336 offers a new therapeutic avenue with a distinct mechanism of action that could provide durable disease control without the need for ongoing immunosuppression.
