Quizartinib refused marketing authorization by EMA CHMP

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has refused marketing authorization to quizartinib for the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) with a FLT3-internal tandem duplication (ITD).1,2 Having reviewed the data presented, the EMA CHMP felt that despite marginal improvement in overall survival (OS), the study had limitations that did not allow the efficacy of quizartinib to be demonstrated sufficiently for approval. They concluded that the benefits did not outweigh the risks and refused the marketing authorization.1

In May 2019, quizartinib was also rejected by the United States (US) Food & Drug Administration (FDA). The FDA Oncologic Drug Advisory Committee voted 8–3 against approval of the new drug application (NDA) and raised questions regarding the generalizability and credibility of the data.3 Quizartinib had previously been granted orphan drug designation by the EMA and breakthrough therapy designation by the FDA.4,5

Clinical Trials6

The results from the QuANTUM-R trial, which assessed the value of quizartinib compared to investigator’s choice of salvage chemotherapy, were recently published in Lancet Oncology.

Given as quizartinib vs salvage chemotherapy

  • Median OS: 6.2 vs 4.7 months
  • Estimated 12-month survival: 27% vs 20%
  • Hazard ratio for progression or death: 0.76, 95% CI: 0.58–0.92, p= 0.02
  • Treatment-emergent deaths: 33% vs 17%

This study concluded quizartinib monotherapy conferred a survival benefit compared to salvage chemotherapy, with a manageable safety profile for patients with FLT3-ITD R/R AML.

The ongoing QuANTUM-First study (NCT02668653) is evaluating quizartinib plus standard chemotherapy followed by quizartinib monotherapy will benefit patients with newly diagnosed AML.

  1. European Medicines Agency. Refusal of the marketing authorisation for Vanflyta (quizartinib). https://www.ema.europa.eu/en/documents/smop-initial/questions-answers-refusal-marketing-authorisation-vanflyta-quizartinib_en.pdf [Accessed 2019 Oct 22]
  2. European Medicines Agency. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 14-17 October 2019. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-14-17-october-2019. [Accessed 2019 Oct 22]
  3. OncLive. FDA Panel Votes Against Quizartinib for AML. https://www.onclive.com/web-exclusives/fda-panel-votes-against-quizartinib-approval-for-aml [Accessed 2019 Oct 22]
  4. European Medicines Agency. EU/3/09/622. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu309622-0. [Accessed 2019 Oct 22]
  5. BioSpace: FDA Grants Breakthrough Therapy Designation to Daiichi Sankyo's FLT3 Inhibitor Quizartinib for Relapsed/Refractory FLT3-ITD AML. 2018 Aug 01. https://www.biospace.com/article/releases/fda-grants-breakthrough-therapy-designation-to-daiichi-sankyo-s-flt3-inhibitor-quizartinib-for-relapsed-refractory-flt3-itd-aml/ [Accessed 2019 Oct 22]
  6. Cortes J.E. et al., Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Onc. 2019 Jun 04. DOI: 10.1016/ S1470-2045(19)30150-0

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