Takeda Pharmaceutical Company Limited announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for its SBECD cyclodextrin enabled investigational drug pevonedistat for the treatment of patients with higher-risk myelodysplastic syndromes (HR-MDS). Pevonedistat, a first in class NEDD8-activating enzyme (NAE) inhibitor, could be the first novel treatment for HR-MDS patients in more than a decade, expanding treatment options that have so far been limited to hypomethylating agent (HMA) monotherapy alone. Even with current treatment options, outcomes for people living with HR-MDS remain poor.
The Breakthrough Therapy Designation is based on the final analysis of the Pevonedistat-2001 Phase 2 study, which evaluated pevonedistat plus azacitidine versus azacitidine alone in patients with rare leukemias, including HR-MDS. The FDA considered a number of endpoints, including overall survival (OS), event-free survival (EFS), complete remission (CR) and transfusion independence, as well as the adverse event profile. This designation signals a potential advancement in addressing the needs of people living with HR-MDS, for whom few therapies exist and the benefits are limited.
Breakthrough Therapy Designation from the U.S. FDA is granted to accelerate the development and regulatory review of investigational drugs that are intended to treat serious or life-threatening ailments. Agents with this designation have shown preliminary clinical evidence that indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Takeda presented results of the Pevonedistat-2001 trial during oral sessions at the virtual 56th American Society of Clinical Oncology (ASCO) Annual Meeting and virtual 25th European Hematology Association (EHA) Annual Congress.
Pevonedistat is a first in class NEDD8-activating enzyme (NAE) inhibitor. In pre-clinical studies, the inhibition of NAE by pevonedistat blocked the modification of select proteins, which resulted in disruption of cell cycle progression and cell survival, leading to cancer cell death. Pevonedistat in combination with azacitidine demonstrated promising clinical activity in a Phase 2 study of patients with higher-risk myelodysplastic syndromes (HR-MDS), higher-risk chronic myelomonocytic leukemia (HR-CMML) and acute myeloid leukemia (AML) and a Phase 1 study of patients with AML. Pevonedistat is currently being evaluated in Phase 3 studies as a first-line treatment for patients with HR-MDS, HR-CMML and AML, who are ineligible (unfit) for transplant or intensive induction chemotherapy, and in a Phase 2 study in unfit AML in a triple combination with azacitidine and venetoclax. Pevonedistat is an investigational drug for which safety and efficacy have not been established.