Menin Inhibitor Enzomenib Gains FDA Orphan Drug Designation in ALL

The FDA has granted orphan drug designation to enzomenib (DSP-5336), an investigational, oral, small molecule menin inhibitor in development for the treatment of patients with acute lymphoblastic leukemia (ALL).¹

The designation builds on a prior orphan drug designation awarded to the agent for treatment of acute myeloma leukemia (AML) in 2022.¹ The FDA's orphan drug program is designed to support development of therapies for rare diseases or conditions, offering incentives intended to encourage sponsors to pursue indications that might otherwise attract limited investment.

“The availability and selection of treatment choices is a major clinical and logistical challenge for patients with [ALL], a challenge underscored by the complexity of sequencing therapies,” Tsutomu Nakagawa, president and CEO of Sumitomo Pharma America, stated in a news release.¹ “Receiving [o]rphan [d]rug [d]esignation for enzomenib for the treatment of ALL is an exciting development that reinforces the molecule’s potential. We will work closely with the FDA to advance clinical research of enzomenib in the hopes of bringing an innovative new treatment option to people living with ALL.”

Enzomenib: A New Entrant Among Menin Inhibitors

Enzomenib is an investigational, oral, small molecule inhibitor that disrupts the interaction between menin and the lysine (K)-specific methyltransferase 2A (KMT2A) protein, an interaction implicated in acute leukemia and other malignancies driven by aberrant cell proliferation. In preclinical studies, enzomenib demonstrated selective growth inhibition in human acute leukemia cell lines harboring KMT2A rearrangements or NPM1 mutations. The agent was also shown to reduce expression of the leukemia-associated genes HOXA9 and MEIS1 while increasing expression of CD11b, a marker associated with myeloid differentiation, in these same cell line models.

Current Clinical Development and Next Steps

The clinical development of enzomenib is underway in an ongoing first-in-human phase 1/2 dose-escalation and -expansion study (NCT04988555). The objectives of the study are to evaluate the agent’s safety, pharmacokinetics, pharmacodynamics, and preliminary activity as monotherapy and in combination with other agents, such as venetoclax (Venclexta)-azacitidine, gilteritinib (Xospata), and intensive 7+3 chemotherapy.² The study is enrolling patients globally with relapsed or refractory acute leukemia, including AML, ALL, or acute leukemia of ambiguous lineage, for an estimated total enrollment of 606 patients.

Preliminary data presented at the 2024 European Hematology Association (EHA) Congress showed that as of January 31, 2024, the overall response rate among 22 efficacy-evaluable patients was 45%, with a complete remission (CR) plus CR with partial hematologic recovery rate of 23%.³

In terms of safety, the agent was deemed well tolerated, with the most common treatment-emergent adverse events reported in the overall population (n = 58) being vomiting (15.5%) and nausea (12.1%). No dose-limiting toxicities were observed, and 1 patient experienced asymptomatic QT prolongation that required temporary dose interruption and reduction.

The agent is also being studied in a registrational phase 2 trial, Horizen-1, which is evaluating enzomenib monotherapy in patients with relapsed or refractory AML or ALL harboring KMT2A rearrangements or NPM1 mutations. In June 2026, the trial had accrued the required number of patients to allow for interim analysis, the results of which are expected by the end of 2026.⁴

REFERENCES

1. Sumitomo Pharma America Announces Enzomenib (DSP-5336) Receives FDA Orphan Drug Designation for Treatment of Acute Lymphoblastic Leukemia. News release. Sumitomo Pharma America. July 30, 2026. Accessed July 30, 2026. https://tinyurl.com/c774h2j2

2. A Phase 1/​2 Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia (Horizen-1). ClinicalTrials.gov. Updated March 24, 2026. Accessed July 30, 2026. https://clinicaltrials.gov/study/NCT04988555

3. Daver N, Erba H, Watts J, et al. First-in-human phase 1/2 study of the menin-MLL inhibitor DSP-5336 in patients with relapsed or refractory acute leukemia: Updated results from dose escalation. Presented at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract S132.

4. Sumitomo Pharma America Achieves Key Patient Enrollment Milestone for Pivotal Phase 2 Study of Enzomenib in the Treatment of Relapsed/Refractory Acute Leukemia. News release. Sumitomo Pharma America. June 10, 2026. Accessed July 30, 2026. https://tinyurl.com/4bapvzae