Pharmaceutical Business review

Takeda gets FDA breakthrough therapy status for pevonedistat to treat higher-risk HR-MDS

The head office of Takeda Pharmaceutical Company, in Chuo-ku, Osaka, Japan (Credit: GFDL, Cc-by-sa-2.5)

MDS is a rare form of bone marrow-related cancer, which will be resulted due to irregular blood cell production within the bone marrow.

Pevonedistat, a first-in-class NEDD8-activating enzyme (NAE) inhibitor, is claimed to be the first novel treatment for HR-MDS patients in more than a decade.

The FDA has granted the status based on the final analysis of the Pevonedistat-2001 Phase 2 study that assessed pevonedistat plus azacitidine plus azacitidine alone in patients with rare leukaemias, including HR-MDS.

According to the company, the FDA studied various endpoints, including overall survival (OS), event-free survival (EFS), complete remission (CR) and transfusion independence, as well as the adverse event profile.

Takeda oncology therapeutic area unit head Christopher Arendt said: “Higher-risk MDS is associated with poor prognosis, diminished quality of life and a higher chance of transformation to acute myeloid leukaemia, another aggressive cancer.

“The combination of pevonedistat and azacitidine is a promising therapeutic approach with the potential to be the first novel treatment advancement for higher-risk MDS in more than 10 years.”

In pre-clinical studies, the inhibition of NAE by pevonedistat prevented the modification of select proteins, helping to disrupt the cell cycle progression and cell survival and cause cell death.

Pevonedistat in combination with azacitidine showed significant clinical activity in a phase 2 study of patients with higher-risk myelodysplastic syndromes (HR-MDS), higher-risk chronic myelomonocytic leukaemia (HR-CMML) and acute myeloid leukaemia (AML) and a Phase 1 study of patients with AML, said the company.

At present, pevonedistat is being assessed in phase 3 studies as a first-line treatment for patients with HR-MDS, HR-CMML and AML, who are ineligible for transplant or intensive induction chemotherapy.

It is also being evaluated in a Phase 2 study in unfit AML in a triple combination with azacitidine and venetoclax.

In June, Takeda has entered into a more than $2bn worth deal with Neurocrine Biosciences to develop potential therapies for psychiatric disorders.