FDA fast tracks Sumitomo Pharma's DSP-5336 for AML

The United States Food and Drug Administration (FDA) has awarded fast track designation to DSP-5336, an investigational treatment developed by Sumitomo Pharma America (SMPA), for patients with relapsed or refractory acute myeloid leukemia (AML). This designation aims to expedite the development and review process for DSP-5336, highlighting its potential in addressing a critical medical need.

DSP-5336 is a small molecule inhibitor that specifically targets interactions between menin and mixed lineage leukemia (MLL) proteins, which play significant roles in gene expression and biological pathways associated with cell growth and hematopoiesis. The drug's mechanism is designed to disrupt these protein interactions, thereby influencing the proliferation of leukemia cells.

SMPA is currently conducting a Phase I/II clinical trial to assess the safety and efficacy of DSP-5336 in patients suffering from relapsed or refractory AML characterized by either mixed lineage leukemia rearrangement (MLLr) or nucleophosmin mutation (NPM1m). In preclinical studies, DSP-5336 has demonstrated selective inhibition of growth in human acute leukemia cell lines bearing KMT2A (MLL) rearrangements or NPM1 mutations. Additionally, the drug has shown to affect the expression of leukemia-associated genes and promote differentiation in these cell lines.

The ongoing clinical trial focuses on dose escalation and dose expansion to determine the optimal dosing regimen. The treatment has been well-tolerated among participants, with no dose-limiting toxicities reported. Moreover, there have been no significant cardiac issues or treatment-related discontinuations or deaths. DSP-5336 has also exhibited minimal drug-drug interactions with azoles, a class of antifungal medications, and repeat dosing has resulted in little to no pharmacokinetic accumulation.

The trial has yielded promising results, with objective response rates observed in 57% of patients. Notably, 24% of the participants achieved complete remission or complete remission with partial hematologic recovery. These outcomes are particularly significant for patients with NPM1 mutations and MLL rearrangements, who currently have limited targeted treatment options.

Jatin Shah, Chief Medical Officer of SMPA's oncology division, emphasized the challenges in managing AML and the scarcity of approved targeted therapies for patients with specific genetic alterations like KMT2A (MLL) rearrangements or NPM1 mutations. He highlighted the promising clinical activity of DSP-5336 and the potential of menin inhibitors to significantly improve outcomes for these patients. Shah expressed optimism about the early trial results and the FDA's fast track designation, underscoring the importance of collaborative efforts to advance DSP-5336 swiftly. The ultimate goal is to provide a well-tolerated and effective treatment option for individuals battling relapsed or refractory acute myeloid leukemia.