Taking A Closer Look at Gilteritinib for R/R FLT3 Mutation-Positive AML Patients

In a recent interview at the 2018 ASCO Meeting, Rare Disease Report^® sat down with Steven Benner, MD, MHS, senior vice president and global therapeutic area head of Oncology, discusses the use of gilteritinib in patients with relapsed/refractory FLT3 mutation-positive acute myeloid leukemia (AML).

Rare Disease Report^® (RDR^®): Could you discuss the phase 3 trial of gilteritinib for patients with relapsed/refractory FLT3 mutation-positive AML?

Benner: What we presented at ASCO this time was a trial-in-progress, so it’s a trial that’s actually recruiting patients, but we don’t yet have the results available for it. That’s a trial we are doing in collaboration with a bone marrow transplant called clinical trial network where we’re taking patients with AML who have undergone a stem cell transplant and are treating them with gilteritinib. [Gilterinitib is] a FLT3 mutant inhibitor for patients with AML the FLT3 mutation occurs in about 30% of AML patients, and when it’s present, it confers a worse prognosis.

This trial will allow us to see whether or not in the future we can hopefully extend the use of gilteritinib into patients who are undergoing a stem cell transplant, which is the definitive therapy for the disease.

We also just recently announced that we had received a priority review for our initial filing for gilteritnib; that will be in patients with a relapse refractory FLT3 positive AML. That’s called the “Admiral Study,” and we filed with both the Japanese PMDA and the US FDA using interim results from a planned analysis looking at both the complete remission and the CRH rate as the co-primary endpoint. That trial continues because we’re also following those patients for overall survival. We don’t yet have the outcomes of that study to present.

(RDR^®): What are the primary challenges AML patients face, and how does gilteritinib help them overcome some of them?

Benner: Patients with AML have been found to have a series of different mutations that are important for driving the disease. One of the most common is the FLT3 mutation which occurs in about 30% of AML patients. When it occurs, it means those patients have more aggressive disease they are more likely to relapse and when they relapse, unfortunately, they do very poorly.

Consequently, our therapy is an oral therapy which will allow us to target that specific mutation and it targets both the most common form—which is an internal tandem duplication of the mutation—but also a terminal mutation, which is what is associated with resistance to therapy. Our drug targets both of those types of FLT3 mutations. Since it’s a potent inhibitor, it has also been able to induce complete remissions, including deep molecular responses in patients that have received it as a single agent.

(RDR^®): What are the next steps for the drug?

Benner: Just at the very end of April, we were able to announce that we have submitted a [New Drug Application] to both the Pharmaceutical and Medical Devices Agency (PMD) in Japan and the US Food and Drug Administration (FDA) in March. We now know that as of last week that filing has been accepted by the FDA and that it’s going to undergo a priority review, which hopefully means that the review time will be shorter than the FDA’s typical metrics. So, we find that very encouraging in hopes of bringing our drugs to the patients as soon as possible.

(RDR^®): If this drug is approved, what will the clinical implications be?

Benner: This would be the first flit-3 inhibitor approved for the treatment of FLT3 positive AML in the relapse refractory setting. We’re also doing a series of trials that will bring it into the earlier stages of the disease as well.