Rigel Presents Updated Data from the Ongoing Phase 1b Study Evaluating R289 in Patients with Lower-Risk MDS at the 67th ASH Annual Meeting and Exposition
Key highlights from the updated data as of October 28, 2025, include:
- 33 patients were enrolled, representing a difficult-to-treat population. The median age was 75. The median number of prior therapies was 3 (range: 1-8); 76% (25) of patients had received luspatercept, 73% (24) had received an erythropoiesis stimulating agent (ESA), 67% (22) had received an hypomethylating agent (HMA) and 6% (2) had received imetelstat. 61% (20) of patients were high transfusion burden (HTB) at baseline. 67% (22) of patients were ring sideroblast (RS) negative.
- Median duration of treatment was 5.5 months (range: 0.9 - 27.7 months). R289 was generally well tolerated across all dose groups in this heavily pre-treated lower-risk MDS patient population, the majority of whom were HTB at baseline. The most common Grade 1/2 treatment-emergent adverse events (TEAEs) (in ≥18% of patients) were diarrhea (n=10, 30%), constipation and fatigue (each n=9, 27%), and creatinine increased and cough (each n=7, 21%). The most frequent Grade 3/4 TEAEs were anemia (n=6, 18%), neutrophil count decreased and pneumonia (each n=5, 15%), and alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased (each n=3, 9%). One (1) dose limiting toxicity (DLT) (Grade 4 AST increased/Grade 3 ALT increased) was reported in the 750 mg dose group.
- For evaluable transfusion dependent (TD) patients (≥16 weeks follow up) at dose levels of at least 500 mg QD and higher, 6/18 (33%) patients achieved durable red blood cell transfusion independence (RBC-TI) of >8 weeks [500 mg QD (1/3), 750 mg QD (2/5), 500/250 mg QD (1/5), 500 mg BID (2/5)]. Duration of RBC-TI was >16 weeks in 4 patients and >24 weeks in 3 patients. The median time to onset of RBC-TI was 1.9 months and the median duration of RBC-TI was 22.9 weeks. Peak hemoglobin increases of 2.9 to 6.1 g/dL compared to baseline occurred in patients achieving RBC-TI.
- Of the 6 patients achieving RBC-TI, 5 had received an HMA.
- At doses ≥500 mg QD, steady state R835 plasma concentrations reached or exceeded those associated with 50-90% inhibition of lipopolysaccharide (LPS)-induced cytokine release previously observed in healthy volunteers.
2025-12-07T00:00:00Z Read more