FDA Grants Astellas Pharma Inc Priority Review for Gilteritinib for Refractory AML

Today, the US Food and Drug Administration (FDA) has accepted Astellas Pharma Inc’s New Drug Application (NDA) for gilteritinib for the treatment of adult patients with relapsed or refractory (resistant to treatment) acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. The NDA was accepted with Priority Review.

Previously, Astellas Pharma submitted its NDA application this past April. In October, Rare Disease Report^® spoke with Steven Benner, MD, senior vice president and global therapeutic area head, Oncology Development, Astellas, in an exclusive interview regarding gilteritinib.

“Gilteritinib is a compound we’re very excited about; it was actually developed internally at Astellas by our colleagues in Japan,” Benner told RDR.

Gilteritinib is a novel, small molecule inhibitor of the tyrosine kinases FLT3/AXL.

“We’ve developed, primarily the FLT3 inhibitor,” Benner said. “FLT3 is a very common mutation—40% of all patients with AML will have this mutation. When it’s present, it’s a driver mutation, so patients who have this mutation have a greater likelihood of having relapse, and when they relapse, the survival is worse than in patients without the mutation.” It’s both a target and a driver of outcomes, he added.

The drug is currently in Phase 3 development, and preclinical studies have exhibited its superior antitumor effects when administered with chemotherapy treatment of cytarabine (AraC) and either daunorubicin (DNR) or idarubicin (IDR) compared with combination chemotherapy.

AML is a rare cancer that affects the blood and bone marrow in which excess, immature white blood cells accumulate.

"FLT3 mutations impact approximately 30% of AML patients and are often associated with poor survival outcomes. Many with this condition relapse after treatment or don't respond to currently available treatments. Simply put, they need more options," commented Benner in a recent statement. "The FDA's acceptance of this NDA, with Priority Review, represents a significant milestone for gilteritinib and Astellas in our mission to help AML patients and the physicians who treat them."

The ongoing phase 3 ADMIRAL trial, which is investigating gilteritinib for the treatment of adult patients with FLT3mut+ relapsed or refractory AML, serves as the basis for the drug’s NDA.

Gilteritinib was also previously granted both Orphan Drug designation and Fast Track designation by the FDA in addition to receiving Orphan Designation from the European Commission (EC) and Orphan Drug Designation from the Japan Ministry of Health, Labor and Welfare (MHLW). SAKIGAKE designation was also granted to gilteritinib for relapsed/refractory AML by the Ministry of Health, Labor, and Welfare (MHLW) in Japan.

The Phase 3 ADMIRAL trial is an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The overall survival and complete remission (CR) / CR with partial hematological recovery (CRh) rate are the co-primary endpoints of the ongoing trial.

The current primary outcomes measures include the relapse-free survival (RFS), which will be measured from the time of randomization up to 61 months or until documented relapse or death from any cause occurs. Relapse after CR will be defined as bone marrow blasts of 5% or greater, any circulating blasts, and/or any extra-medullary blast foci as per Revised International Working Group (IWG) criteria. An independent review committee will determine relapse events and conduct efficacy assessments unless specifically stated otherwise.

Three hundred and seventy-one participants with FLT3 mutations present in their bone marrow or whole blood, as determined by central lab, are currently enrolled in the study. Participants have been randomized in a 2:1 ratio to be administered oral gilteritinib (120 mg) or salvage chemotherapy. The current estimated primary completion date for the study is March 2024.

Looking forward, November 29^th, 2018, is the Prescription Drug User Fee Act (PDUFA) action date for a decision by the FDA.

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