Takeda Pharmaceutical has reported that its investigational drug, pevonedistat, in combination with azacitidine failed to meet the primary goal of the Phase III Panther (Pevonedistat-3001) clinical trial in patients with rare leukaemias.

A NEDD8-activating enzyme (NAE) inhibitor, pevonedistat can interrupt protein homeostasis and subsequently lead to cancer cell death.

The trial analysed if pevonedistat combination as first-line therapy could boost event-free survival (EFS) in patients with higher-risk myelodysplastic syndromes (HR-MDS), chronic myelomonocytic leukaemia (CMML) and low-blast acute myeloid leukaemia (AML) compared with azacitidine alone.

Death or change to AML in higher-risk MDS or CMML patients, whichever happens first, and death in AML patients, were defined as an event in the trial.

Data showed that the PANTHER trial did not meet the pre-defined statistical significance for EFS.

Furthermore, the safety profile of the combination therapy was in line with already reported results.

Takeda Pharmaceutical oncology cell therapy and therapeutic area unit head Chris Arendt said: “While we are disappointed with this outcome, we are continuing to gain a greater understanding of the full data set and hope that findings from this Phase III study will provide information to help guide research and development for potential treatment options for these underserved patient populations.”

The company notified the investigators of the results and will work with them to decide on the suitable action for patients who are part of the trial.

In July 2020, the US Food and Drug Administration granted breakthrough therapy status to pevonedistat to treat HR-MDS patients.

The combination therapy was demonstrated to be a very active, favourable treatment approach in the Phase II Pevonedistat-2001 trial.

It had also indicated benefit in the HR-MDS subgroup across various clinically meaningful endpoints such as overall survival, EFS, complete remission and transfusion independence.

Takeda reported positive data from the Phase III trial assessing recombinant von Willebrand factor prophylaxis for von Willebrand disease in July 2021.

Cell & Gene Therapy Coverage on Clinical Trials Arena supported by Cytiva.

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