– DSP-5336, an Investigational Menin and
Mixed-lineage Leukemia Inhibitor, is Being Evaluated in Patients
with Relapsed or Refractory Acute Myeloid Leukemia (AML) with a
mixed lineage leukemia rearrangement (MLLr) or nucleophosmin
mutation (NPM1m) –
MARLBOROUGH, Mass., July 15,
2024 /PRNewswire/ -- Sumitomo Pharma America,
Inc. (SMPA) today announced that the U.S. Food and Drug
Administration (FDA) granted Fast Track designation to DSP-5336 for
the treatment of patients with relapsed or refractory acute myeloid
leukemia (AML) with a KMT2A rearrangement, also known as, mixed
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 interaction,
which plays key roles in gene expression and protein interactions
involved in many biological pathways, including cell growth, cell
cycle, genomic stability, and hematopoiesis.1,2,3
FDA Fast Track Designation is granted to investigational
therapies being developed to treat serious or life-threatening
conditions that demonstrate the potential to address unmet medical
needs.
"For patients and families facing a diagnosis of relapsed or
refractory acute myeloid leukemia, significant unmet medical needs
remain – and we share in their urgency to identify and advance new
treatment pathways," said Tsutomu
Nakagawa, Ph.D, President and Chief Executive Officer of
SMPA. "We are encouraged by FDA's decision and look forward to
working closely with the agency as we continue our clinical
development of DSP-5336."
Updated data from the ongoing open-label, dose escalation and
optimization portion of the Phase 1/2 study for DSP-5336 were
presented at the European Hematology Association (EHA) 2024
Hybrid Congress, building on preliminary data presented at the
2023 American Society of Hematology (ASH) Annual Meeting. Objective
response was observed in 57% (12/21) of patients, which included
responses in patients with both Nucleophosmin 1 (NPM1) mutation and
KMT2A (MLL) rearrangement. The proportion with complete
remission or complete remission with partial hematologic recovery
(CR/CRh) was 24% (5/21 patients).
To date, DSP-5336 remains well-tolerated with no dose limiting
toxicity (DLT) observed and no significant cardiac signal nor
treatment-related discontinuations or deaths. No significant
drug-drug interactions with azoles have been identified and repeat
dosing results in minimal to no pharmacokinetic accumulation.
Importantly, no differentiation syndrome (DS) prophylaxis was
needed, and the three cases of DS reported (5%) were manageable and
did not result in intensive care unit (ICU) stays or
discontinuation of DSP-5336.
"Management of AML continues to be challenging with limited
options for which there are currently no approved targeted
therapies to treat AML with KMT2A (MLL) rearrangements or NPM1
mutations, leaving a serious unmet medical need," said Jatin Shah, M.D., Chief Medical Officer –
Oncology at SMPA. "DSP-5336 has shown promising clinical activity,
and menin inhibitors have tremendous potential to impact the
outcomes of these types of acute leukemia. We are excited by these
early results and FDA Fast Track Designation, and look forward to
working closely with the agency and our collaborators to rapidly
advance this program with the goal of providing a well-tolerated
and effective targeted treatment option for patients with relapsed
or refractory acute myeloid leukemia."
Leukemia is a type of cancer that forms in blood-forming tissue,
characterized by the uncontrolled growth of blood cells, usually
white blood cells, in the bone marrow. Acute leukemia, a form of
leukemia, requires immediate treatment as blood cells multiply
rapidly leading to a sudden onset of symptoms.4
Approximately 30% of AML patients have NPM1 mutations6
and 5-10% of AML patients 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 interaction. Menin is a scaffold nuclear protein
which plays key roles in gene expression and protein interactions
involved in many biological pathways, including cell growth, cell
cycle, genomic stability, and hematopoiesis.1,2 In
preclinical studies, DSP-5336 has shown selective growth inhibition
in human acute leukemia cell lines with KMT2A (MLL) rearrangements
or NPM1 mutations.1,3 DSP-5336 reduced the expression of
the leukemia-associated genes HOXA9 and MEIS1, and increased the
expression of the differentiation gene CD11b in human acute
leukemia cell lines with MLL rearrangements and NPM1
mutation.7,8 The safety and efficacy of DSP-5336 is
currently being clinically evaluated in a Phase 1/2 dose
escalation/dose expansion study in patients 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 Fast Track 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 global pharmaceutical company based
in Japan with key operations in
the U.S. (Sumitomo Pharma America, Inc.), Canada (Sumitomo Pharma Canada, Inc.) and
Europe (Sumitomo Pharma
Switzerland GmbH) focused on addressing patient needs in oncology,
urology, women's health, rare diseases, psychiatry & neurology,
and cell & gene therapies. With several marketed products in
the U.S., Canada, and Europe, a diverse pipeline of early- to
late-stage assets, and in-house advanced technology capabilities,
we aim to accelerate discovery, research, and development to bring
novel therapies to patients sooner. For more information on SMPA,
visit our website https://www.us.sumitomo-pharma.com or follow us
on LinkedIn.
SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd.,
used under license.
Sumitomo Pharma America, Inc. is a U.S. subsidiary of Sumitomo
Pharma Co., Ltd.
© 2024 Sumitomo Pharma America, Inc. All rights reserved.
For a copy of this release, visit Sumitomo Pharma
America's website at www.us.sumitomo-pharma.com.
|
References
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- Eguchi K, Shimizu T, Kato D, et al. Preclinical Evaluation of a
Novel Orally Bioavailable Menin-MLL Interaction Inhibitor,
DSP-5336, for the Treatment of Acute Leukemia Patients with
MLL-Rearrangement or NPM1 Mutation.
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https://doi.org/10.1182/blood-2021-152050.
- Daver N, Zeidner JF, Yuda J, et al. Phase 1/2 First-in-Human
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https://doi.org/10.1182/blood-2023-179252.
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