Evaluation of Obexelimab in Patients with Warm Autoimmune Hemolytic Anemia: Preliminary Results from an Open Label Phase 2 Study

Introduction. Warm autoimmune hemolytic anemia (wAIHA) is a rare, serious autoimmune disorder characterized by the binding of autoantibodies to red blood cells (RBCs) at core body temperature (37°C), leading to hemolysis and signs/symptoms of anemia, including severe fatigue, dyspnea, pallor, and jaundice. There are currently no FDA-approved treatments for wAIHA, and anemia is typically managed with corticosteroids. Relapse is common and long-term steroid use carries significant risk of side effects and other complications. There is a need for new, safe and effective therapies. Obexelimab is a bifunctional, non-depleting humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B-lineage cell activity. Obexelimab is an investigational product and not approved for any indication. Here we report on the safety and efficacy of obexelimab in an open-label Phase 2 study in patients with wAIHA (NCT05786573).

Methods. The ongoing, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamic (PD), and efficacy (including improvement in hemoglobin (Hgb)) of obexelimab in patients with wAIHA. The study is expected to enroll 14 patients with primary or secondary wAIHA due to autoimmune disorders. Eligible patients are 18 years of age or older, have been clinically diagnosed with wAIHA for at least 3 months with documentation of a positive direct antiglobulin test and have failed at least 1 previous wAIHA therapy. Patients must have at least one sign/symptom of anemia with a hemoglobin level of ≥ 7 to < 10 g/dL on Day 1. Eligible patients self-administer obexelimab via weekly subcutaneous (SC) injections.

Results. Six patients have been enrolled to date. The median age at the time of enrollment was 70.5 years. Other demographics include: 5/6 (83.3%) of patients were female; 5/6 (83.3%) were white; 1/6 (16.7%) was Asian. All patients had a diagnosis of primary wAIHA, and the median disease duration was approximately 3 years. Median Hgb at baseline was 9.50 g/dL, and 4 patients were on background therapy (including glucocorticoids, EPO, mycophenolate) at the time they entered the study.

All 6 patients have been on study for a minimum of 10 weeks (range 10 - 24 weeks). Hemoglobin improvement from baseline have been observed in 3 of the 6 patients.

Four out of 6 patients (67%) experienced a total of 18 treatment emergent adverse events (TEAEs). 3 TEAEs were considered related, and all these were grade 1. There was one serious and not related event of cholecystitis. There were no discontinuations due to adverse events.

Conclusions. Data from the ongoing study suggests that obexelimab administered SC is well-tolerated and may provide improvement in Hgb and other biomarkers of anemia in patients with primary wAIHA, who have failed at least one prior therapy.

Fattizzo:Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Agios Pharmaceuticals, Inc.: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Evans:AstraZeneca: Honoraria. Wells:Zenas BioPharma: Current Employment. Poma:Zenas BioPharma: Current Employment. Quinn:Zenas BioPharma: Current Employment. Zhang:Zenas BioPharma: Current Employment. Yamashita:Zenas BioPharma: Current Employment. Fischer:Zenas BioPharma: Current Employment.