On September 15, 2025 Akeso Inc. (9926.HK) reported that its proprietary next-generation humanized IgG4 monoclonal antibody targeting CD47, ligufalimab (AK117), has been granted Orphan Drug Designation (ODD) by the U.S. FDA for the treatment of acute myeloid leukemia (AML) (Press release, Akeso Biopharma, SEP 15, 2025, View Source [SID1234655979]).

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The Orphan Drug Designation is a program established by the FDA to incentivize the development of therapies for rare diseases. Drugs with this designation benefit from comprehensive FDA guidance during development, tax incentives, and up to seven years of market exclusivity upon approval.

Akeso is actively advancing the international clinical development for ligufalimab, which is being evaluated in both hematologic malignancies and solid tumors. In addition to its application in AML, patient enrollment has been completed in a randomized, double-blind, multicenter Phase II study assessing ligufalimab combined with azacitidine in higher-risk myelodysplastic syndromes (HR-MDS).

Ligufalimab is also the first CD47 monoclonal antibody to enter registrational Phase III trials in solid tumors. Two Phase III studies are currently ongoing: one evaluating the combination of ligufalimab and ivonescimab as first-line treatment for PD-L1-positive head and neck squamous cell carcinoma (HNSCC), and another study assessing this combination as first-line therapy for pancreatic cancer.

Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal proliferation of myeloid blasts in the bone marrow, peripheral blood, and extramedullary tissues. It is the most common type of acute leukemia in adults. Treatment strategies for AML, as outlined in the NCCN Guidelines, are primarily based on whether patients are eligible for intensive induction chemotherapy. For those ineligible for such chemotherapy, treatment options remain limited.

The FDA has currently approved venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine for newly diagnosed AML patients aged 75 years or older, or for those with comorbidities that preclude intensive chemotherapy. However, more than half of these patients relapse within 6–9 months, with a median overall survival of approximately one year, highlighting a significant unmet clinical need.

Ligufalimab is a humanized IgG4 monoclonal antibody that binds specifically to CD47 expressed on tumor cells, blocking its interaction with the SIRPα receptor. This disrupts the "don’t eat me" signal, thereby enhancing macrophage-mediated phagocytosis of tumor cells and inhibiting tumor growth. Ligufalimab’s unique design prevents red blood cell agglutination and demonstrates significantly improved safety and efficacy compared to other CD47-targeting agents.

Preclinical studies have shown that ligufalimab, when combined with azacitidine or venetoclax, synergistically enhances the expression of "eat me" signals (such as calreticulin), leading to more efficient activation of phagocytic immune responses. This combination may thus offer a promising treatment option for AML patients ineligible for standard induction chemotherapy.

Clinical trials have demonstrated that ligufalimab combined with azacitidine shows a favorable safety profile and promising efficacy in first-line AML treatment. Even at high doses (up to 45 mg/kg, administered biweekly), ligufalimab was well tolerated, with no significant safety differences observed across patient groups. The complete remission (CR) rate at the target dose reached 50%, and the composite complete remission (cCR) rate was 55%.

Building on these encouraging results, Akeso has launched a Phase II study to further investigate the safety and efficacy of ligufalimab in combination with venetoclax and azacitidine for first-line AML patients ineligible for intensive chemotherapy.