Sumitomo Pharma Unveils New DSP-5336 Data at 2024 EHA Congress

Sumitomo Pharma America, Inc. (SMPA) has announced promising results from their ongoing Phase 1/2 clinical trial of DSP-5336, an investigational menin and mixed-lineage leukemia (MLL) inhibitor. The data were presented at the European Hematology Association (EHA) 2024 Hybrid Congress. The clinical trial focuses on DSP-5336's efficacy in treating patients with relapsed or refractory acute leukemia, a severe condition characterized by the rapid proliferation of abnormal blood cells.

DSP-5336 functions as a small molecule inhibitor targeting the interaction between menin and MLL proteins, which are crucial in various biological pathways such as cell growth regulation and genomic stability. The trial's preliminary data were initially shared at the American Society of Hematology (ASH) Annual Meeting in 2023. The recent EHA presentation provided updated findings from the trial's dose escalation and optimization phase, which includes patients treated with DSP-5336 administered orally in 28-day cycles at doses ranging from 40 mg to 300 mg twice daily.

The EHA presentation highlighted results from 57 patients, with more consistent responses observed in those receiving at least 140 mg twice daily. In particular, 21 patients with either Nucleophosmin 1 (NPM1) mutations or KMT2A (MLL) rearrangements showed significant improvement. Among these patients, 57% exhibited an objective response, including 24% who achieved complete remission or complete remission with partial hematologic recovery.

To date, DSP-5336 has demonstrated a favorable safety profile, with no dose-limiting toxicity observed. Additionally, there were no significant cardiac issues, treatment-related discontinuations, or deaths associated with the drug. The investigational therapy has also shown minimal pharmacokinetic accumulation and no significant drug-drug interactions with azoles. Importantly, differentiation syndrome (DS) prophylaxis was not necessary, and the few cases of DS reported were manageable without requiring intensive care or discontinuation of the treatment.

Dr. Naval Daver, Director of the Leukemia Research Alliance Program at The University of Texas MD Anderson Cancer Center, emphasized the potential of DSP-5336. He noted that the drug's high objective response rate and favorable safety profile in relapsed or refractory acute leukemia patients are encouraging. Menin inhibitors like DSP-5336 could significantly improve outcomes by reversing the leukemogenic activity associated with MLL fusion and mutated NPM1 proteins.

Acute leukemia is a rapidly progressing cancer that originates in blood-forming tissues, leading to the uncontrolled growth of abnormal blood cells. Acute myeloid leukemia (AML), a common type of acute leukemia, often requires immediate intervention. Approximately 30% of AML patients have NPM1 mutations, while 5-10% have KMT2A (MLL) rearrangements. Despite advancements in treatment, there remains a significant unmet need for targeted therapies for these specific genetic abnormalities.

Dr. Jatin Shah, Chief Medical Officer – Oncology at SMPA, highlighted the importance of menin inhibition in treating acute leukemia. He expressed optimism about the early results from the DSP-5336 study, hoping to provide an effective and well-tolerated treatment option for patients with AML. The ongoing study aims to further investigate DSP-5336's potential to improve patient outcomes and advance care for those battling this aggressive form of leukemia.

In conclusion, DSP-5336 represents a promising investigational therapy for relapsed or refractory acute leukemia, particularly for patients with NPM1 mutations or KMT2A (MLL) rearrangements. The data presented at the EHA 2024 Hybrid Congress suggest that DSP-5336 is well-tolerated and efficacious, offering hope for improved treatment options in this challenging medical landscape.