Daiichi Sankyo in pursuit of Novartis’ Rydapt with next-generation FLT3 drug

Novartis’ FLT3 inhibitor Rydapt was a much-welcomed addition to the armamentarium against acute myeloid leukemia when it was approved last year. Now, Daiichi Sankyo has data that could allow it to file its new-generation rival for approval.

The Japanese drugmaker’s quizartinib candidate—acquired as part of its $410 million takeover of San Diego biotech Ambit Biosciences in 2014—has become the first drug in the class to improve overall survival compared with chemotherapy in relapsed or refractory AML with FLT3-ITD mutations, regardless of whether they have received a stem cell transplant.

The FLT3 gene mutation is one of the most common genetic abnormalities in individuals with AML, and FLT3-ITD is the most common FLT3 mutation, affecting around 25% of patients and associated with a particularly aggressive form of the cancer.

The data from the QuANTUM-R isn’t available to view just yet, but Daiichi Sankyo has said it can move ahead with regulatory filings for quizartinib as a second-line option for AML. It will still have work to do before it can tackle Rydapt (midostaurin) head-on, however, as Novartis’ drug—which inhibits FLT3 but also other kinases—is currently approved for use alongside chemo in newly-diagnosed patients.

Rydapt’s approval for AML was a landmark for the 30% more so of patients who have FLT3 mutations, providing the first targeted treatment option for a disease that has been treated for decades mainly with chemotherapy after the FDA gave it a green light a year ago. Since then it’s been joined on the market by another targeted therapy, Celgene’s Idhifa (enasidenib), although this targets AML patients with IDH mutations.

Rydapt has flaws: Its scattergun approach to kinase inhibition means it has side effects, and it is not approved for use on its own as monotherapy trials have yielded disappointing results.

Oncologists think next-generation FLT3s like quizartinib have the potential to move into the front-line setting in AML, both alone and in combination with chemo, and so start to muscle in on Rydapt’s territory. Daiichi Sankyo is carrying out a phase 3 trial in previously-untreated patients called QuANTUM-First that is due to report in 2020.

Other candidates in the next-gen FLT3 inhibitor category include Astellas' gilteritinib, which was submitted for FDA approval in relapsed/refractory AML last month and Arog Pharma's crenolanib which is in late-stage development.

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