On December 15, 2023 Akeso reported two phase Ib clinical results of its innovative CD47 monoclonal antibody ligufalimab (AK117) in combination with azacitidine in patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) and treatment-naïve acute myeloid leukemia (AML) at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Akeso Biopharma, DEC 15, 2023, View Source [SID1234638617]).

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HR-MDS

Anemia is a significant symptom of MDS, and effectively managing anemia and minimizing blood transfusion are crucial aspects of disease control. As of August 25, 2023, a total of 86 patients were evaluable for safety. Anemia (a primary adverse event associated with CD47 blocking antibodies) occurred in only 29.1% of the patients. Of 13 evaluable patients who initially required red blood cell (RBC) transfusions, 61.5% became independent of RBC transfusion.

Among 27 evaluable patients, the complete remission (CR) rate was 48.1% and the overall response rate (ORR) was 85.2%. When patients received≥3 cycles of treatment, the CR rate reached 52%; when patients received≥6 cycles of treatment, the CR rate reached 68.4%. AK117 combination therapy provides patients with rapid and significant remission. The median time to response (mTTR) was 0.97 months and the median time to CR (mTTCR) was 2.92 months.

AK117 is an IgG4 monoclonal antibody targeting CD47 without inducing hemagglutination effects. Therefore, AK117 does not require a lower ‘priming dose’ to prevent anemia. AK117 has emerged as a potential best-in-class therapy for MDS. In this study, AK117 in combination with AZA was well tolerated with low incidence of anemia and demonstrated promising efficacy in patients with newly diagnosed HR-MDS. AK117 is expected to be a superior treatment option for MDS patients worldwide.

Akeso has received FDA clearance for the Investigational New Drug (IND) application for AK117 in combination with azacitidine for the treatment of patients with newly diagnosed higher-risk MDS. This randomized, double-blind, global multi-center Phase II study is underway. Notably, Akeso is consistently advancing the development of AK117 as a therapeutic agent in combination with various agents such as PD-1/CTLA-4 and PD-1/VEGF bispecific antibodies, for the treatment of multiple hematologic malignancies and solid tumors.

AML

As of August 25, 2023, among 20 evaluable patients, the composite complete remission(CCR) rate was 55%, with 50.0% of patients achieving CR.

The combination of AK117 and AZA exhibited a manageable safety profile with a low incidence of anemia, and demonstrated promising efficacy as a first-line treatment in AML patients who were unable to undergo intensive chemotherapy. Akeso is planning to conduct a randomized, open-label, phase II study to evaluate the safety and efficacy of AK117 in combination with venetoclax and AZA in patients with AML unfit for first-line intensive chemotherapy.

About Ligufalimab (AK117)

AK117, independently developed by Akeso, is a next-generation humanized lgG4 anti-CD47 antibody without hemagglutination effect. AK117 can bind to CD47 expressed on tumor cells and block the interaction between CD47 and SIRPα, in order to enhance the phagocytic activity of phagocytes on tumor cells, thereby inhibiting the growth of tumors.

Currently, several phase II clinical trials are underway to investigate the potential of AK117 in combination with azacitidine for hematological tumors, as well as AK117 alone or in combination with PD-1/CTLA-4 and PD-1/VEGF bispecific antibodies for various solid tumors. Preliminary studies have shown promising efficacy and safety profiles of AK117, with no observed dose-limiting toxicity events. Additionally, an international multicenter clinical study evaluating AK117 for the treatment of MDS has been initiated.