Just three days after Daiichi Sankyo’s Xospata challenger scored approval in Japan for a form of acute myeloid leukemia (AML), the FDA has declined to clear the drug in the U.S. The snub comes after a series of troubles for quizartinib, with the FDA pushing back its review timeline by three months and an expert panel voting against approval for the blood cancer med.
The company broke the news in a brief statement Friday, saying only that it had received a complete response letter from the agency for its application for quizartinib as a treatment for adults with relapsed or refractory AML with the FLT3-ITD mutation. The FLT3 mutation is one of the most common mutations in people with AML, with FLT3-ITD affecting about 25% of patients.
"Daiichi Sankyo is evaluating the Complete Response Letter and will determine next steps in the U.S.," Antoine Yver, M.D., who heads oncology R&D at Daiichi Sankyo, said in the statement.
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Daiichi picked up quizartinib five years ago when it snapped up San Diego-based Ambit Biosciences in a deal worth up to $410 million. Before that, Ambit had been working with Daiichi’s compatriot Astellas under a $40 million pact inked in 2009 around quizartinib and other FLT3 inhibitors. Astellas walked away in 2013—on the eve of Ambit’s IPO, no less—taking the $350 million it promised with it.
In May 2018, data showing quizartinib lengthened AML patients’ lives over chemotherapy gave Daiichi the confidence to go ahead with an FDA filing for the drug as a second-line treatment. It landed priority review status in November.
Last April, the FDA moved the PDUFA date for quizartinib back three months to Aug. 25 to have more time to review additional data it had requested from Daiichi. The company’s shares dipped 1.5% on the news, but Daiichi didn’t bat an eyelid.
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“We remain confident in the data supporting our NDA submission and are committed to bringing quizartinib forward as a potential treatment for relapsed or refractory FLT3-ITD AML, a particularly aggressive and difficult-to-treat subtype of AML, where patients need additional targeted treatment options," Arnaud Lesegretain, vice president of oncology R&D and head of the AML franchise at Daiichi, said at the time.
But it only got worse for quizartinib. Last month, an FDA advisory committee voted 8-3 against recommending quizartinib for approval after agency officials outlined concerns about the reliability of the phase 3 data in a briefing document ahead of the meeting.
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“FDA seeks input from the committee on whether the imbalance in early censoring and patients randomized but not treated between the arms on Study AC220-007, the inconsistency of the results across the stratification subgroups and the effects of subsequent therapies on the primary endpoint impact the interpretation of the study results to a degree that renders them unreliable,” the agency wrote in the briefing materials.