Takeda Launches Phase III Clinical Trial of NAE Inhibitor Pevonedistat in Combination with Azacitidine for High-Risk Myelodysplastic Syndromes, CMML, and Low-Blast AML

Fengqiu

Source:PharmaCube Info

On October 14, the Drug Clinical Trial Registration and Information Publicity Platform showed that Takeda Pharmaceutical Company Limited initiated a Phase III clinical study of its NAE inhibitor Pevonedistat in combination with azacitidine for the treatment of higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) with low blast counts.

Source: Drug Clinical Trial Registration and Information Publicity Platform

The primary objective of this trial is to determine whether the combination of pevonedistat and azacitidine improves event-free survival (EFS) compared with azacitidine monotherapy. (In patients with myelodysplastic syndromes [MDS] or chronic myelomonocytic leukemia [CMML], an event is defined as death or transformation to acute myeloid leukemia [AML], whichever occurs first; in patients with low-blast AML, an event is defined as death.) EFS: time from randomization to the occurrence of an EFS event (for patients with MDS or CMML, an EFS event is defined as death or transformation to AML, whichever occurs first; for patients with low-blast AML, the event is defined as death).

Pevonedistat is a small-molecule inhibitor of NEDD8-activating enzyme (NAE), used for the treatment of myelodysplastic syndromes, various leukemias, and tumors. NEDD8-activating enzyme (NAE) is the rate-limiting enzyme in the neddylation pathway. Inhibition of NAE activity reduces the activity of the ubiquitin-proteasome system (UPS) pathway and the degradation of related proteins, thereby inducing apoptosis in tumor cells. Compared with proteasome inhibitors, NAE inhibitors exhibit greater specificity in disrupting intracellular homeostasis.

In addition, there is an NAE inhibitor TAS4464 developed by Taiho Pharmaceutical that is in Phase I clinical trials.