Massachusetts-based Sumitomo Pharma America, Inc. (SMPA) has secured US FDA orphan drug designation for enzomenib (DSP-5336) in acute lymphoblastic leukemia (ALL), extending the regulatory profile of its oral menin inhibitor beyond acute myeloid leukemia (AML), where it already holds orphan status. The designation adds procedural advantages — including seven years of market exclusivity upon potential approval and eligibility for fee waivers — as the company advances enzomenib through a registrational Phase II trial that includes both AML and ALL patients.
Enzomenib is an oral, small molecule inhibitor of the interaction between menin and lysine (K)-specific methyltransferase 2A (KMT2A). That protein-protein interaction drives leukemogenic gene expression in tumors harboring KMT2A rearrangements (KMT2Ar) or NPM1 mutations (NPM1m). In preclinical studies, enzomenib reduced expression of the leukemia-associated genes HOXA9 and MEIS1 and increased expression of the differentiation marker CD11b in human acute leukemia cell lines carrying those genetic alterations.
The ALL designation follows orphan drug status previously granted for AML in June 2022 and a Fast Track designation for relapsed or refractory AML with KMT2Ar or NPM1m granted in June 2024. Japan's Ministry of Health, Labour and Welfare also granted orphan status for the AML indication in September 2024. Enzomenib is currently being evaluated in two ongoing studies: a Phase I/II dose-escalation and dose-expansion study in patients with relapsed or refractory acute leukemia (NCT04988555), and the registrational Phase II Horizen-1 study, which enrolls patients with relapsed or refractory AML or ALL carrying KMT2Ar or NPM1m.
ALL is an aggressive malignancy characterized by overproduction of lymphocytes in the bone marrow, with rapid progression if untreated. Treatment sequencing in the relapsed or refractory setting remains a clinical challenge, with limited options available to patients who have exhausted standard therapies. Other programs in the relapsed or refractory ALL space include Allterum Therapeutics' anti-CD127 monoclonal antibody 4A10, which entered Phase I in May 2026, illustrating the range of mechanisms under investigation. Within the menin inhibitor class, revumenib has received US FDA approval in relapsed or refractory KMT2Ar acute leukemia, making the competitive positioning of enzomenib in both AML and ALL dependent on differentiated efficacy or safety data from the Horizen-1 readout.