FDA Fast Tracks Sumitomo Pharma's DSP-5336 for Relapsed/Refractory AML

Sumitomo Pharma America, Inc. (SMPA) has announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to DSP-5336, an investigational treatment for patients with relapsed or refractory acute myeloid leukemia (AML) characterized by a KMT2A rearrangement, also known as mixed lineage leukemia rearrangement (MLLr), or a nucleophosmin mutation (NPM1m). DSP-5336 is a small molecule inhibitor targeting the interaction between menin and mixed-lineage leukemia (MLL) proteins, crucial in regulating gene expression and other vital biological processes such as cell growth, cell cycle, genomic stability, and hematopoiesis.

The FDA's Fast Track Designation is designed to expedite the development of treatments for serious or life-threatening conditions that address unmet medical needs. Tsutomu Nakagawa, Ph.D., President and CEO of SMPA, expressed optimism about the FDA's decision and emphasized the company's commitment to advancing DSP-5336 through clinical development.

Recent data from an ongoing Phase 1/2 clinical trial for DSP-5336 were presented at the European Hematology Association (EHA) 2024 Hybrid Congress. These data built on preliminary findings shared at the 2023 American Society of Hematology (ASH) Annual Meeting. The study showed that 57% (12 out of 21) of patients achieved an objective response, including patients with both NPM1 mutations and MLL rearrangements. The complete remission rate or complete remission with partial hematologic recovery (CR/CRh) was observed in 24% (5 out of 21) of patients.

So far, DSP-5336 has been well-tolerated by patients, with no dose-limiting toxicity or significant cardiac issues reported. There were no treatment-related discontinuations or deaths. Additionally, no significant drug-drug interactions with azoles were identified, and repeated dosing did not lead to significant pharmacokinetic accumulation. Notably, no differentiation syndrome (DS) prophylaxis was needed, and the three reported cases of DS (5%) were manageable without requiring intensive care unit (ICU) stays or discontinuation of the treatment.

Jatin Shah, M.D., Chief Medical Officer – Oncology at SMPA, highlighted the challenges of managing AML and the limited options available for treating AML with KMT2A rearrangements or NPM1 mutations. He noted that DSP-5336 has shown promising clinical activity and emphasized the potential of menin inhibitors to improve outcomes for these types of acute leukemia. Shah expressed excitement about the early results and the FDA Fast Track Designation and mentioned the company's dedication to collaborating with the FDA and other partners to advance DSP-5336 rapidly.

Leukemia, a type of cancer affecting blood-forming tissues, leads to the uncontrolled growth of blood cells, usually white blood cells, in the bone marrow. Acute leukemia, a more severe form, requires immediate treatment due to the rapid multiplication of blood cells, causing a sudden onset of symptoms. Approximately 30% of AML patients have NPM1 mutations, and 5-10% have KMT2A rearrangements.

DSP-5336 is an investigational small molecule inhibitor targeting the menin and MLL protein interaction, crucial for gene expression and various biological pathways. In preclinical studies, DSP-5336 demonstrated selective growth inhibition in human acute leukemia cell lines with KMT2A rearrangements or NPM1 mutations. The treatment reduced the expression of leukemia-associated genes HOXA9 and MEIS1 and increased the expression of the differentiation gene CD11b in these cell lines. The safety and effectiveness of DSP-5336 are currently being evaluated in a Phase 1/2 clinical trial. The FDA granted Orphan Drug Designation for DSP-5336 in June 2022 and Fast Track Designation in June 2024 for treating relapsed or refractory acute myeloid leukemia with MLLr or NPM1m.