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Updated Data Presented for R289 in Lower-Risk MDS

Rigel Pharmaceuticals recently presented updated data from their ongoing Phase 1b study evaluating R289, an oral prodrug aimed at treating patients suffering from lower-risk myelodysplastic syndrome (MDS). The findings, revealed during a session at the 67th American Society of Hematology (ASH) Annual Meeting, are particularly significant for elderly patients with complex medical histories.

Overview of R289

R289 functions as a potent and selective dual inhibitor of interleukin receptor-associated kinases 1 and 4, abbreviated as IRAK1/4. This compound's development aims to address the unmet medical needs prevalent in patients who have experienced relapses or failed previous treatments. Presenting the results was Dr. Guillermo Garcia-Manero, who highlighted the critical nature of these findings amid ongoing treatment uncertainties for this patient demographic.

In the study, 33 patients were enrolled, all from a notably challenging pool—an average age of 75, with many having undergone multiple prior therapies. A staggering 76% had previously received treatments like luspatercept or erythropoiesis-stimulating agents. Given these conditions, R289 was shown to generally be well tolerated, with only a modest incidence of attention-worthy adverse events.

Key Findings

Among evaluable patients undergoing at least 16 weeks of follow-up while receiving R289 at doses of 500 mg once daily (QD) or higher, a significant finding was that 33% achieved durable red blood cell transfusion independence (RBC-TI) for over eight weeks. Five of the six patients who reached RBC-TI had received hypomethylating agents (HMAs) prior—an encouraging sign for future applications of R289.

The drug's side effects were predominantly mild, with common issues including diarrhea, fatigue, and increased creatinine levels. However, serious effects occurred and were categorized under Grades 3 and 4, such as anemia and pneumonia. One notable dose-limiting toxicity was reported in the higher dose category, displaying the need for continued monitoring as studies progress. Regardless, the success of achieving RBC-TI suggests the potential efficacy of R289 in this setting.

Anticipating Future Steps

Moving forward, Rigel Pharmaceuticals is planning to finalize the phase of dose expansion in this study, with a recommended Phase 2 dose targeted for selection in the latter half of 2026. R289 was previously acknowledged for its Orphan Drug designation and has received Fast Track designation from the FDA, which propels its position as a significant candidate for developing therapies aimed at managing lower-risk MDS.

Dr. Lisa Rojkjaer, the chief medical officer of Rigel, offered an optimistic outlook regarding the drug's future. "New therapies are needed for patients with transfusion-dependent lower-risk MDS. We are pleased to share these updated study results, which underscore the potential of R289 to become a viable treatment option for these patients." As the company moves ahead, the ramifications for patients currently living with this ailment could be profound. Rigel's ongoing research, especially with compounds such as R289, embodies a pivotal step toward enhancing the therapeutic landscape for those affected by hematological disorders and cancer.

Conclusion

The findings from this Phase 1b study provided at ASH are a testament to Rigel Pharmaceuticals' commitment to improving treatment options for lower-risk MDS patients. With its continued evolution and exploration in clinical trials, R289 may indeed pave the way for a new chapter in managing this challenging condition. The anticipation surrounding the final recommendations for the Phase 2 doses reflects the hope that lies ahead for many patients who have long awaited effective treatment solutions.