The FDA has granted orphan drug designation to enzomenib for acute lymphoblastic leukemia.
The FDA has granted orphan drug designation to investigational, small molecule, oral menin inhibitor enzomenib (DSP-5336) as a potential therapeutic option for the treatment of patients with acute lymphoblastic leukemia (ALL).1
Enzomenib is currently being evaluated in the phase 1/2 Horizen-1 trial (NCT04988555) for patients with relapsed/refractory ALL, which includes a registrational phase 2 portion evaluating the agent as monotherapy in patients with relapsed/refractory ALL or acute myeloid leukemia harboring a KMT2A rearrangement or NPM1 mutation.
The regulatory decision marks the second orphan drug designation granted to enzomenib, following a 2022 designation in AML, in addition to a
Early data from the trial showed that patients who received at least daily 140-mg doses of enzomenib with relapsed/refractory AML harboring NPM1 mutations or KMT2A rearrangements (n = 21) achieved an overall response rate of 57%.3 Additionally, these patients experienced a 25% complete response (CR) or CR with partial hematologic recovery (CRh) rate.
Early data also demonstrated that nzomenib was well tolerated among patients with no cardiac adverse effects, dose-limiting toxicities, or deaths reported.
“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, PhD, president and chief executive officer of Sumitomo Pharma America, stated in a news release.1 “Receiving orphan drug designation 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.”
The open-label, dose-escalation/dose-expansion study is enrolling patients who are at least 18 years of age or at least 12 years of age and weigh at least 40 kg with relapsed/refractory acute leukemia.4 KMT2A rearrangements or NPM1 mutations were not needed for all patients, although they were required in regions or countries where indicated by regulatory authorities. Patients also need to have an ECOG performance status of 2 or less, a life expectancy of at least 3 months, and a creatinine clearance level of at least 50 mL/min.
If patients have a left ventricular ejection fraction lower than 50%, have acute promyelocytic leukemia, have central nervous system leukemia, received calcineurin inhibitors within 2 weeks of their first dose, or underwent hematopoietic stem cell transplantation or CAR T-cell therapy within 60 days of their first dose, they cannot enroll in the trial.
Patients are receiving oral enzomenib either as monotherapy or in combination with other treatments like venetoclax (Venclexta), azacitidine, and gilteritinib (Xospata).
Primary end points of the study are identifying the recommended phase 2 dose of enzomenib, as well as safety, CR/CRh rates. Secondary end points for the trial include ORR, overall survival, and event-free survival.
The phase 2 monotherapy study of enzomenib is reported to have completed enrollment for a prespecified interim analysis, with results expected by the end of 2026.5 If the primary end point is met, regulatory submissions targeting approval in the US and Japan are expected in 2027.1
“Acute leukemias, especially at the relapsed/refractory stage, are profoundly difficult to treat, and are associated with very poor outcomes,” Nakagawa said in the news release. “Achieving this enrollment milestone is an important step in our efforts to bring a new, differentiated therapeutic option to acute leukemia patients and their families.”
