Daiichi Sankyo Receives Negative CHMP Opinion for Vanflyta (Quizartinib) in Relapsed/Refractory FLT3-ITD AML

Oct 23, 2019 14:27 CST Updated 14:27

Daiichi-Sankyo

Pharmaceutical R&D Developer

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

Daiichi Sankyo recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a negative opinion recommending against approval of the Marketing Authorization Application (MAA) for Vanflyta (quizartinib), an oral targeted anticancer drug, for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). Regarding U.S. regulatory matters, the Food and Drug Administration (FDA) extended the review period for Vanflyta’s New Drug Application (NDA) by three months in April this year, until August 25, 2019. According to the statement released at that time, the FDA required additional time to review supplementary data submitted by Daiichi Sankyo in response to FDA requests. However, in June this year, the FDA issued a Complete Response Letter (CRL), refusing to approve Vanflyta.

Vanflyta received approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) in June this year, marking its first regulatory approval worldwide. Earlier this month, Vanflyta was launched on the market in Japan. This approval in Japan is based on data from the global pivotal Phase III clinical study QuANTUM-R and a Phase II clinical study conducted in Japanese patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML).

Notably, the QuANTUM-R study is the first randomized Phase III trial to demonstrate that a FLT3 inhibitor, as an oral monotherapy, significantly prolongs overall survival compared with chemotherapy in patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). In this study, Vanflyta oral monotherapy significantly reduced the risk of death by 24% compared with salvage chemotherapy (HR=0.76, p=0.0177, 95% CI: 0.58–0.98) and significantly prolonged overall survival (median OS: 6.2 months [two-sided 95% CI: 5.3–7.2] vs. 4.7 months [two-sided 95% CI: 4.0–5.5]). The estimated 1-year survival rate was 27% in the Vanflyta group versus 20% in the salvage chemotherapy group. Regarding safety, the most common adverse drug reactions in patients treated with Vanflyta were nausea (33.2%, 80/241), QT interval prolongation on electrocardiogram (24.9%, 60/241), anemia (24.9%, 60/241), and thrombocytopenia (21.2%, 51/241). Data from a Japanese Phase II study showed that the prespecified primary endpoint of complete response rate was met at the interim analysis. The efficacy and safety profile of Vanflyta in this study were consistent with those observed in the QuANTUM-R study.

Antoine Yver, MD, Executive Vice President and Global Head of Oncology R&D at Daiichi Sankyo, stated: “While we are disappointed by the CHMP’s opinion, we will evaluate the feedback received from the CHMP to determine the next steps for Vanflyta in treating patients with relapsed/refractory FLT3-ITD AML in Europe. Despite this setback, we remain confident in the potential benefits of Vanflyta for patients with FLT3-ITD AML, and we look forward to the results of the global pivotal Phase III QuANTUM-First study, which is evaluating Vanflyta in combination with chemotherapy in patients with newly diagnosed FLT3-ITD AML. We remain committed to bringing Vanflyta as a potential treatment option for this aggressive and difficult-to-treat AML subtype in the United States, Europe, and other regions worldwide.”

The active pharmaceutical ingredient of Vanflyta, quizartinib, is a second-generation FLT3 inhibitor. This drug is an oral small-molecule receptor tyrosine kinase inhibitor that selectively targets and inhibits FLT3. In the United States, quizartinib has been granted Breakthrough Therapy designation by the FDA for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML), as well as Fast Track designation for the treatment of relapsed/refractory AML. Furthermore, quizartinib has been granted orphan drug designation for the treatment of AML in both the United States and the European Union, and in Japan, it has received orphan drug designation for the treatment of FLT3-mutated AML.

Acute myeloid leukemia (AML) is an aggressive cancer of the blood and bone marrow, characterized by the uncontrolled proliferation and accumulation of dysfunctional leukemic white blood cells, which impairs the production of normal blood cells. FLT3 gene mutations are among the most common genetic abnormalities in AML, with FLT3 internal tandem duplication (FLT3-ITD) being the most prevalent FLT3 mutation, affecting approximately one-quarter of AML patients. FLT3-ITD is a driver mutation associated with high leukemic burden and poor prognosis, significantly impacting disease management in AML patients. Compared with AML patients without the FLT3-ITD mutation, those with FLT3-ITD have a poorer overall prognosis, including increased rates of relapse, higher risk of death following relapse, and a greater likelihood of relapse after hematopoietic stem cell transplantation.

Original Source: Daiichi Sankyo Receives Negative CHMP Opinion for FLT3 Inhibitor Quizartinib for Treatment of Patients with Relapsed/Refractory FLT3-ITD AML

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