FDA Grants Gilteritinib Fast Track Designation for FLT3-positive AML

The US Food and Drug Administration (FDA) granted Fast Track designation to gilteritinib for the treatment of adult patients with FLT3-positive (FLT3+) relapsed or refractory (R/R) acute myeloid leukemia (AML).¹

Gilteritinib inhibits the FLT3 mutations observed in up to one-third of patients with AML, FLT3 internal tandem duplication (ITD), and the FLT3 tyrosine kinase domain (TKD). Gilteritinib has also demonstrated inhibitory effects against AXL, which is associated with resistance mechanisms in AML.

Previous studies provided encouraging evidence of clinical efficacy. For the phase 1/2 CHRYSALIS trial, researchers evaluated the safety, efficacy, and tolerability of gilteritinib in 166 patients with R/R AML.²

Patients in the gilteritinib arm had a 53% overall response rate (ORR) regardless of previous treatment, and patients who were previously treated with a TKI had an ORR of 48%. An ORR of 56% was observed in patients who had an FLT3-ITD mutation.

Median overall survival (OS) was approximately 31 weeks (95% CI, 24-35).

The most frequently reported adverse events were diarrhea and fatigue. Grade 3 or greater QTc prolongation was observed in 3% of patients.

The phase 3 ADMIRAL trial (ClinicalTrials.gov Identifier: NCT02421939) is investigating the effect of gilteritinib vs salvage chemotherapy in patients with R/R AML.

Fast Track designation is granted to investigational drugs that treat serious and life-threatening conditions, allowing for greater accessibility to the FDA and may lead to expedited review, development, and entry to market.

References

1. U.S. FDA grants Fast Track designation to Astellas for development of gilteritinib in relapsed or refractory acute myeloid leukemia [news release]. Tokyo, Japan: Astellas; October 11, 2017. http://newsroom.astellas.us/2017-10-10-U-S-FDA-Grants-Fast-Track-Designation-to-Astellas-for-Development-of-Gilteritinib-in-Relapsed-or-Refractory-Acute-Myeloid-Leukemia. Accessed October 11, 2017.
2. Exploratory analysis of the phase I/II CHRYSALIS study of gilteritinib demonstrates first molecular response to FLT3 inhibitor in acute myeloid leukemia [news release]. Northbrook, IL: Astellas; June 6, 2017. http://newsroom.astellas.us/2017-06-06-Exploratory-Analysis-of-the-Phase-I-II-CHRYSALIS-Study-of-gilteritinib-Demonstrates-First-Molecular-Response-to-FLT3-Inhibitor-in-Acute-Myeloid-Leukemia. Accessed October 11, 2017.