To give the FDA more time to evaluate updates to quizartinib’s proposed REMS program, the regulator is pushing the target action date to July 24.
Pictured: FDA Headquarters/Courtesy Grandbrothers/Adobe Stock
Thursday, the FDA pushed back its target action date by three months for Daiichi Sankyo’s investigational acute myeloid leukemia (AML) drug quizartinib, citing updates to the proposed Risk Evaluation and Mitigation Strategies (REMS).
The FDA has until July 24 to determine whether it will grant approval for the drug. The regulator did not request additional safety or efficacy data to support quizartinib’s regulatory bid.
The delay will allow the FDA to review the changes to quizartinib’s REMS program, Jennifer Brennan, a Daiichi Sankyo company spokesperson, told BioSpace via email.
“A REMS will help inform healthcare professionals about the appropriate use of quizartinib,” Brennan said.
Daiichi Sankyo is seeking approval for quizartinib in AML patients bearing a specific genetic mutation called FLT3-ITD. In the proposed indication, quizartinib will be combined with standard cytarabine and anthracycline for induction and standard cytarabine for consolidation, followed by quizartinib as a monotherapy.
The company backed the candidate’s New Drug Application (NDA), which the FDA accepted in October 2022 with data from the Phase III QuANTUM-First trial. Patients treated with the quizartinib regimen saw a 22.4% reduction in the risk of death compared to those who were given chemotherapy alone.
After nearly 40 months of follow-up, the quizartinib regimen more than doubled the median overall survival versus chemotherapy.
As for safety, QuANTUM-First found a generally manageable adverse event profile, with no new concerning signals observed, Brennan said. Fatal treatment-emergent adverse events were reported in 11.3% of the quizartinib-treated patients, mostly due to infections.
Regulatory Hurdles for the FLT3 Inhibitor
Quizartinib is an orally available small molecule candidate that targets and inhibits the FLT3 protein, a tyrosine kinase receptor found on hematopoietic stem cells. Under healthy circumstances, FLT3 promotes cell survival, growth and differentiation.
The FLT3-ITD mutation is the most common FLT3 mutation in AML, present in about 25% of all newly diagnosed patients. This genetic change is linked to poorer survival rates and a higher risk of relapse.
Daiichi Sankyo had previously submitted an NDA for quizartinib using data from the Phase III QuANTUM-R trial. In the study, the FLT3 inhibitor, given as a single agent, significantly improved overall survival in patients with relapsed/refractory AML. These data earned quizartinib the FDA’s Breakthrough Therapy designation in August 2018.
However, in May 2019, the Oncologic Drugs Advisory Committee voted 8–3, recommending against the approval of quizartinib. Citing several safety concerns, including neutropenia, hypokalemia and thrombocytopenia, the panel of external experts found that quizartinib’s efficacy benefits could not outweigh its risks.
A month later, the FDA followed the advice of the committee and rejected quizartinib.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com
