Sumitomo Pharma Proclaims that DSP-5336 Has Obtained FDA Quick Monitor Designation for the Therapy of Relapsed or Refractory Acute Myeloid Leukemia

– DSP-5336, an Investigational Menin and Blended-lineage Leukemia Inhibitor, is Being Evaluated in Sufferers with Relapsed or Refractory Acute Myeloid Leukemia (AML) with a combined lineage leukemia rearrangement (MLLr) or nucleophosmin mutation (NPM1m) –

MARLBOROUGH, Mass., July 15, 2024 /PRNewswire/ — Sumitomo Pharma America, Inc. (SMPA) at this time introduced that the U.S. Meals and Drug Administration (FDA) granted Quick Monitor designation to DSP-5336 for the remedy of sufferers with relapsed or refractory acute myeloid leukemia (AML) with a KMT2A rearrangement, also called, combined lineage leukemia rearrangement (MLLr) or nucleophosmin mutation (NPM1m). DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interplay, which performs key roles in gene expression and protein interactions concerned in lots of organic pathways, together with cell progress, cell cycle, genomic stability, and hematopoiesis.^1,2,3

FDA Quick Monitor Designation is granted to investigational therapies being developed to deal with severe or life-threatening circumstances that reveal the potential to handle unmet medical wants.

“For sufferers and households dealing with a analysis of relapsed or refractory acute myeloid leukemia, important unmet medical wants stay – and we share of their urgency to establish and advance new remedy pathways,” stated Tsutomu Nakagawa, Ph.D, President and Chief Government Officer of SMPA. “We’re inspired by FDA’s choice and stay up for working carefully with the company as we proceed our scientific growth of DSP-5336.”

Up to date information from the continued open-label, dose escalation and optimization portion of the Part 1/2 examine for DSP-5336 had been introduced on the European Hematology Affiliation (EHA) 2024 Hybrid Congress, constructing on preliminary information introduced on the 2023 American Society of Hematology (ASH) Annual Assembly. Goal response was noticed in 57% (12/21) of sufferers, which included responses in sufferers with each Nucleophosmin 1 (NPM1) mutation and KMT2A (MLL) rearrangement.  The proportion with full remission or full remission with partial hematologic restoration (CR/CRh) was 24% (5/21 sufferers).

To this point, DSP-5336 stays well-tolerated with no dose limiting toxicity (DLT) noticed and no important cardiac sign nor treatment-related discontinuations or deaths. No important drug-drug interactions with azoles have been recognized and repeat dosing ends in minimal to no pharmacokinetic accumulation. Importantly, no differentiation syndrome (DS) prophylaxis was wanted, and the three circumstances of DS reported (5%) had been manageable and didn’t end in intensive care unit (ICU) stays or discontinuation of DSP-5336.

“Administration of AML continues to be difficult with restricted choices for which there are at present no accredited focused therapies to deal with AML with KMT2A (MLL) rearrangements or NPM1 mutations, leaving a severe unmet medical want,” stated Jatin Shah, M.D., Chief Medical Officer – Oncology at SMPA. “DSP-5336 has proven promising scientific exercise, and menin inhibitors have great potential to affect the outcomes of these kind of acute leukemia. We’re excited by these early outcomes and FDA Quick Monitor Designation, and stay up for working carefully with the company and our collaborators to quickly advance this program with the objective of offering a well-tolerated and efficient focused remedy possibility for sufferers with relapsed or refractory acute myeloid leukemia.”

Leukemia is a sort of most cancers that varieties in blood-forming tissue, characterised by the uncontrolled progress of blood cells, normally white blood cells, within the bone marrow. Acute leukemia, a type of leukemia, requires speedy remedy as blood cells multiply quickly resulting in a sudden onset of signs.⁴ Roughly 30% of AML sufferers have NPM1 mutations⁶ and 5-10% of AML sufferers have KMT2A (MLL) rearrangements.⁵

About DSP-5336 
DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interplay. Menin is a scaffold nuclear protein which performs key roles in gene expression and protein interactions concerned in lots of organic pathways, together with cell progress, cell cycle, genomic stability, and hematopoiesis.^1,2 In preclinical research, DSP-5336 has proven selective progress inhibition in human acute leukemia cell strains with KMT2A (MLL) rearrangements or NPM1 mutations.^1,3 DSP-5336 lowered the expression of the leukemia-associated genes HOXA9 and MEIS1, and elevated the expression of the differentiation gene CD11b in human acute leukemia cell strains with MLL rearrangements and NPM1 mutation.^7,8 The protection and efficacy of DSP-5336 is at present being clinically evaluated in a Part 1/2 dose escalation/dose enlargement examine in sufferers with relapsed or refractory acute leukemia (NCT04988555). The FDA granted Orphan Drug Designation for DSP-5336 for the indication of acute myeloid leukemia in June 2022. The FDA granted Quick Monitor Designation for DSP-5336 for the indication of relapsed or refractory acute myeloid leukemia with MLLr or NPM1m in June 2024.

About Sumitomo Pharma
Sumitomo Pharma Co., Ltd. is a worldwide pharmaceutical firm based mostly in Japan with key operations within the U.S. (Sumitomo Pharma America, Inc.), Canada (Sumitomo Pharma Canada, Inc.) and Europe (Sumitomo Pharma Switzerland GmbH) centered on addressing affected person wants in oncology, urology, ladies’s well being, uncommon illnesses, psychiatry & neurology, and cell & gene therapies. With a number of marketed merchandise within the U.S., Canada, and Europe, a various pipeline of early- to late-stage property, and in-house superior know-how capabilities, we intention to speed up discovery, analysis, and growth to carry novel therapies to sufferers sooner. For extra info on SMPA, go to our web site https://www.us.sumitomo-pharma.com or observe us on LinkedIn.

SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd., used underneath license.
Sumitomo Pharma America, Inc. is a U.S. subsidiary of Sumitomo Pharma Co., Ltd.

© 2024 Sumitomo Pharma America, Inc. All rights reserved.

References

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2. Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Traits Biochem Sci. 2013; 38(8):394-402. doi:10.1016/j.tibs.2013.05.005.
3. Kuhn MWM, Music E, Feng Z, et al. Focusing on chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia. Most cancers Discov. 2016;6(10):1166-1181. doi:10.1158/2159-8290.CD-16-0237.
4. Chennamadhavuni A, Lyengar V, Mukkamalla SKR, et al. Leukemia. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Obtainable from: https://www.ncbi.nlm.nih.gov/books/NBK560490/.
5. Borkin D, Klossowski S, Pollock J, et al. Complexity of Blocking Bivalent Protein-Protein Interactions: Growth of a Extremely Potent Inhibitor of the Menin-Blended-Lineage Leukemia Interplay. J Med Chem. 2018;61(11):4832-4850. doi:10.1021/acs.jmedchem.8b00071.
6. Brandi ML, Agarwal SK, Perrier ND, Strains KE, Valk GD, Thakker RV. A number of Endocrine Neoplasia Sort 1: Newest Insights. Endocr Rev. 2021;42(2):133-170. doi:10.1210/endrev/bnaa031
7. Eguchi Ok, Shimizu T, Kato D, et al. Preclinical Analysis of a Novel Orally Bioavailable Menin-MLL Interplay Inhibitor, DSP-5336, for the Therapy of Acute Leukemia Sufferers with MLL-Rearrangement or NPM1 Mutation. Blood 2021; 138 (Complement 1): 3339. Obtainable at: https://doi.org/10.1182/blood-2021-152050.
8. Daver N, Zeidner JF, Yuda J, et al. Part 1/2 First-in-Human Examine of the Menin-MLL Inhibitor DSP-5336 in Sufferers with Relapsed or Refractory Acute Leukemia. Blood 2023; 142 (Complement 1): 2911. Obtainable at: https://doi.org/10.1182/blood-2023-179252. 

SOURCE Sumitomo Pharma America