Ligufalimab Nets FDA Orphan Drug Designation in AML

Ligufalimab (AK117) has received orphan drug designation from the FDA for the treatment of patients with acute myeloid leukemia (AML).1

Findings from a phase 1b/2 study (NCT04980885) demonstrated that response-evaluable patients with AML who received ligufalimab at the recommended phase 2 dose (RP2D) of 30 mg/kg every 2 weeks in combination with azacitidine (Vidaza; n = 20) achieved a complete remission (CR) rate of 50.0% and a composite CR (cCR) rate of 55.0%.2 The partial response and CR with incomplete hematologic rates were both 5%. The median time to CR was 1.84 months (range, 1.0-2.9) and the median time to response was 1.17 months (range, 0.9-2.7).

Ligufalimab is a next-generation humanized IgG4 monoclonal antibody that specifically binds to CD47 on tumor cells, blocking its interaction with the SIRPα receptor.1 The agent is designed to prevent red blood cell agglutination. Findings from a preclinical study have shown that ligufalimab in combination with azacitidine or venetoclax (Venclexta) synergistically enhances the expression of "eat me" signals, leading to more efficient activation of phagocytic immune responses, according to a news release from Akeso, the manufacturer of ligufalimab.

What Was the Design of the Phase 1b/2 Study?

The multicenter, open-label trial enrolled adult patients 18 years and older with AML, a life expectancy of at least 3 months, and adequate organ function.2 Patients were also required to have an ECOG performance status of 0 to 3; patients who were at least 75 years old needed to have an ECOG performance status of 0 to 2.

Patients received subcutaneous azacitidine at 75 mg/m2 on days 1 through 7 every 4 weeks. Azacitidine was administered intravenously at 10 to 20 mg/kg every week, followed by 30 to 45 mg/kg every 2 weeks. Each cycle was 4 weeks; treatment continued until disease progression, intolerable toxicity, or the start of subsequent anticancer therapy.

The primary end points were cCR rate and safety. Secondary end points included CR rate, time to response, event-free survival, overall survival, and pharmacokinetics.

At baseline, patients treated at the RP2D (n = 22) had a median age of 63 years (range, 37-80). Most patients had an ECOG performance status of 2 (59.1%), AML not otherwise specified (59.1%), and grade 3 or higher anemia (95.5%).

What Was the Safety Profile of Ligufalimab Plus Azacitidine?

In the safety population (n = 43), any-grade treatment-emergent adverse effects (TEAEs) occurred at a rate of 97.7%. One patient was forced to discontinue treatment due to a TEAE. Common any-grade TEAEs included decreased white blood cell count (72.1%), decreased lymphocyte count (60.5%), decreased platelet count (58.1%), decreased neutrophil count (53.5%), constipation (39.5%), vomiting (37.2%), pneumonia (30.2%), and anemia (30.2%). Grade 3 or higher TEAEs included decreased white blood cell count (58.1%), decreased platelet count (48.8%), decreased neutrophil count (48.8%), decreased lymphocyte count (30.2%), and anemia (23.3%).

Ligufalimab is also being evaluated in combination with azacitidine in patients with higher-risk myelodysplastic syndromes in a phase 2 trial (NCT06196203).1 According to Akeso, ligufalimab is the first CD47 monoclonal antibody to enter registrational phase 3 trials; the agent is being evaluated in combination with ivonescimab as first-line treatment for PD-L1-positive head and neck squamous cell carcinoma (NCT06601335) and in combination with ivonescimab as a frontline therapy for the treatment of patients with pancreatic cancer (NCT06953999).

References

1. Akeso’s ligufalimab (CD47 mAb) receives FDA orphan drug designation for acute myeloid leukemia (AML). News release. Akesobio. September 15, 2025. Accessed September 16, 2025. https://www.akesobio.com/en/media/akeso-news/250916/
2. Wang H, Zhang Q, Teng Q, et al. A phase 1b study evaluating the safety and efficacy of AK117 (anti-CD47 monoclonal antibody) in combination with azacitidine in patients with treatment-naïve acute myeloid leukemia. Blood. 2023;142(suppl 1):4280. doi:10.1182/blood-2023-180618