Ligufalimab (AK117), developed by Akeso, is a next-generation humanized IgG4 anti-CD47 monoclonal antibody being investigated for the treatment of myeloid malignancies, including AML and MDS. By blocking the CD47 signal, it is designed to restore macrophage-mediated phagocytosis and enhance anti-tumor immune activity. The agent is being evaluated in combination with azacitidine (AZA), with or without venetoclax (VEN), in patients with treatment-naïve AML and higher-risk MDS who are ineligible for intensive chemotherapy. In September 2025, ligufalimab received FDA Orphan Drug Designation for AML, reinforcing its potential in a high-unmet-need setting.

Ligufalimab is currently in two active Phase II studies across hematologic malignancies, including a global study in first-line MDS (AK117 + AZA) and a China-based study in first-line AML (AK117 + AZA + VEN), with patient enrollment completed in both programs. In the Phase II AML trial, ligufalimab-based combinations have demonstrated improved response depth and encouraging survival trends versus standard therapy, alongside a manageable safety profile consistent with expected hematologic toxicities and no new safety signals observed. As of the data cut-off on November 2025;

Key Efficacy Highlights:

• Composite complete remission (CRc) rate: 56.7% (AK117) vs. 53.3% (Placebo) 

• Overall response rate (ORR): 80.0% vs. 66.7% 

• Measurable residual disease (MRD)-negative CRc among responders: 46.7% vs. 36.7% 

• Median overall survival (OS): Not reached (AK117) vs. 8.3 months (Placebo) 

• 6-month OS rate: 83.3% vs. 73.2% 

• 9-month OS rate: 78.7% vs. 43.1% 

• Median duration of CRc: 10.4 months vs. 6.5 months

Key Safety Highlights:

• Treatment-emergent adverse events (TEAEs): 100% of patients in both arms experienced ≥1 TEAEs 

• Overall TEAEs and serious adverse events (SAEs): Comparable between AK117 and PBO arms 

• Most common TEAEs (AK117 vs PBO): 

• Decreased white blood cell count: 83.3% vs. 83.3% 

• Neutropenia: 80.0% vs. 76.7% 

• Thrombocytopenia: 86.7% vs. 66.7% 

• Hypokalemia: 50.0% vs. 70.0% 

• Grade ≥3 TEAEs: 96.7% vs. 93.3% 

• Treatment discontinuation due to TEAEs: 3 patients vs. 2 patients 

• Fatal TEAEs: 16.7% vs. 30.0% (lower in AK117 arm) 

• Anemia (adverse event of special interest, AESI): 46.7% vs. 50.0% 

• Grade ≥3 anemia: 43.3% in both arms 

• No new safety signals observed with AK117

KOL insights -

“Ligufalimab represents a differentiated CD47-targeting antibody with strong mechanistic and translational rationale in AML, demonstrating effective CD47–SIRPα blockade with preserved antitumor activity and enhanced macrophage-mediated phagocytosis, particularly in combination regimens.” – Expert Opinion

“It represents a major clinical advancement in CD47-targeted therapy by blocking the CD47–SIRPα “don’t eat me” signal while uniquely avoiding the significant red blood cell–related toxicities, including hemagglutination and anemia, that have limited earlier CD47 inhibitors, thereby enabling more complete target engagement with improved tolerability.”– Expert Opinion

Conclusion -

AML is a rare and aggressive blood cancer arising from abnormal bone marrow cells, with about 2,700 new cases diagnosed each year in the UK, most commonly in older adults, particularly those aged 75 years and above. AML in patients who are not eligible for intensive chemotherapy remains difficult to treat, and current standard therapy with venetoclax and azacitidine provides limited long-term disease control, underscoring the need for novel immune-based approaches. AK117, a CD47-targeting monoclonal antibody, is emerging as a promising combination with azacitidine and venetoclax in frontline AML, demonstrating encouraging early efficacy signals alongside a manageable safety profile in Phase II evaluation. As clinical development advances, AK117 has the potential to further validate CD47 blockade as a viable therapeutic strategy in AML and expand treatment options in this high-unmet-need population.