FDA approves Daiichi Sankyo’s new first-line AML drug quizartinib

Patients with a rarer form of acute myeloid leukemia now have a frontline treatment option for the first time, thanks to the FDA’s approval of Vanflyta (quizartinib), Daiichi Sankyo announced late Thursday.

Vanflyta has been approved for FLT3-ITD-positive AML patients in combination with chemo and as a maintenance monotherapy after initial treatment. The agency also approved a companion diagnostic to detect the mutation.

The company pointed out that it’s not indicated as a maintenance monotherapy for patients who had an allogeneic hematopoietic stem cell transplantation and that an improvement in overall survival for those patients wasn’t “demonstrated.”

While AML is one of the most common forms of adult leukemia, up to 37% of those patients will have a FLT3 gene mutation, and approximately 80% of these are FLT3-ITD mutations.

Daiichi hit a roadblock with the FDA in April when the FDA extended the PDUFA date by three months in order to review requested changes to the Risk Evaluation and Mitigation Strategies (REMS) included in the company’s application. The FDA’s REMS program monitors medications with a high potential for serious adverse effects.

Mikkael Sekeres

Mikkael Sekeres, chief of the division of hematology at the University of Miami’s Sylvester Comprehensive Cancer Center and one of the authors of the QuANTUM-First trial, which was the pivotal study that led to this approval, explained to Endpoints News in an interview that the primary endpoint of this large study (median age 56 years old) showed that “at a median follow-up of almost 40 months, median overall survival was 31.9 months on those patients who received quizartinib, versus 15.1 months for those who received placebo.”

“For a long time, for all comers with acute myeloid leukemia, the 5-year overall survival rate is approximately 30%,” Sekeres said, noting that what often lowers the survival is the fact that a lot of patients with AML are diagnosed older and a lot of those patients have poor risk mutations. “So I do think drugs like quizartinib are going to change the natural history of AML,” he said.

Novartis also has a drug approved in 2017 to treat FLT3-mutated AML, known as Rydapt (midostaurin), which was not compared directly to quizartinib in the pivotal trial, Sekeres said. But he said moving forward, the comparator arm for any future trials in this space will have to include either Rydapt or Vanflyta.

Daiichi has been working toward an approval for quizartinib for years as a treatment of FLT3-ITD-positive AML. But its first campaign in refractory AML hit setbacks, including a rejection from the FDA in 2019 after concerns over the drug’s efficacy data. The company did, however, see better data when it moved into earlier-stage patients, and the FDA granted priority review in October 2022.

But the treatment does come with some caveats – a boxed warning for QT prolongation, a heart rhythm disorder, torsades de pointes, another type of fast heart rhythm, and cardiac arrest. Because of these cardiovascular risks, the drug can only be accessed through Vanflyta’s REMS program.

About 14% of patients who took the drug experienced QT prolongation, the company said, including 3% who experienced a grade 3 or 4 event.

Some of the most common adverse reactions were lymphopenia, hypokalemia, hypoalbuminemia, hypophosphatemia and an increase in alkaline phosphatase.

Zachary Brennan contributed reporting to this story.

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