Daiichi Sankyo's Vanflyta Receives First EU Approval for FLT3-ITD AML
EU Approval Enables Entry into the First-Line Treatment Market
On November 6, 2023, the European Union approved Daiichi Sankyo's (4568) Vanflyta (quizartinib) for adult patients with newly diagnosed FLT3-ITD-positive acute myeloid leukemia (AML). The approval covers use in combination with standard cytarabine and anthracycline induction therapy, followed by cytarabine consolidation therapy, and as a single-agent maintenance therapy. This represents a marketed asset, moving beyond the development stage. By enabling use across the induction, consolidation, and maintenance phases, the treatment aims to expand both the duration of treatment and the potential revenue per patient.
Phase 3 Trial Demonstrates More Than Doubling of Overall Survival
The approval is based on the Phase 3 QuANTUM-First trial (NCT02668653), which compared quizartinib in combination with standard therapy versus placebo in 539 patients with newly diagnosed FLT3-ITD-positive AML. The median overall survival (OS) was 31.9 months in the quizartinib arm and 15.1 months in the placebo arm, with a hazard ratio of 0.78 and a p-value of 0.0324. Quizartinib and its major metabolite, AC886, inhibit the autophosphorylation of the FLT3 receptor tyrosine kinase and downstream signaling, thereby suppressing the proliferation of FLT3-ITD-dependent leukemia cells. The survival improvement data provides evidence to support the addition of targeted therapy to existing chemotherapy regimens.
Overcoming Past Regulatory Setbacks with First-Line Data
Quizartinib was initially submitted for approval based on the Phase 3 QuANTUM-R trial in relapsed/refractory AML. However, on May 14, 2019, the FDA Oncology Drugs Advisory Committee (ODAC) voted 8 to 3 against the benefit-risk profile, and the FDA issued a Complete Response Letter (CRL) on June 14. The EMA also rejected the application for the relapsed/refractory indication on October 17, 2019. However, a separate Phase 3 trial in newly diagnosed patients led to approvals in Japan on May 25, 2023, in the US on July 20, 2023, and in the EU on November 6, 2023. This demonstrates how a clinical development strategy that shifted the indication and treatment setting can transform regulatory risk into a commercial asset. In the US, Vanflyta carries a boxed warning and requires a Risk Evaluation and Mitigation Strategy (REMS) due to the risks of QT prolongation, torsade de pointes, and sudden cardiac death.
Direct Competition with Rydapt, Xospata Defends Relapsed Market
The key competitor in the first-line setting is Novartis' (NVS) Rydapt (midostaurin), which inhibits multiple kinases and FLT3, and was approved in the EU on September 20, 2017, for newly diagnosed FLT3-mutated AML. Astellas Pharma's (4503) Xospata (gilteritinib) targets FLT3-ITD and FLT3-TKD and was approved in the EU on October 25, 2019, as a single-agent therapy for relapsed/refractory FLT3-mutated AML, capturing the subsequent line of treatment market. The AML treatment market in the eight major markets is estimated at USD 3.53 billion in 2024, and the speed of Vanflyta's market penetration in Europe will depend on factors such as national reimbursement listings, the availability of FLT3 testing, and the rate of physician switching from Rydapt.
Vanflyta's Phase 3 trial demonstrated a median overall survival of 31.9 months compared to 15.1 months, and a 22% reduction in the risk of death, which strengthens Daiichi Sankyo's antibody-drug conjugate (ADC) oncology revenue base in the USD 3.53 billion AML market across eight major countries. In the short term, competition with Novartis' Rydapt, which has been the standard of care for first-line FLT3-mutated AML in the EU since 2017, will determine the rate of market penetration. For researchers and clinicians, the data provides evidence of the survival benefit of selective FLT3 inhibition across the induction, consolidation, and maintenance phases, but the management of QT prolongation risk and the accessibility of FLT3-ITD companion diagnostics will influence the actual scope of application. In the medium to long term, Vanflyta in the newly diagnosed market and Astellas' Xospata in the relapsed/refractory market will form a competitive landscape across treatment stages, with pricing negotiations in European countries and real-world survival data serving as key indicators of product value.
Source: EMA (ema)