Astellas reports Phase 3 PASHA trial evaluating Xospata (gilteritinib) versus midostaurin in newly diagnosed FLT3-mutated AML failed to meet the primary endpoint of overall survival.
Written By: Sana Khan BPharm
Reviewed By: Pharmacally Editorial Team
Astellas Pharma Inc. and the HOVON Foundation have announced that the Phase 3 HOVON 156 / AMLSG 28-18 / PASHA study (NCT04027309) evaluating Xospata (gilteritinib) versus midostaurin-based therapy in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (FLT3m+ AML) eligible for intensive chemotherapy did not meet its primary endpoint of overall survival (OS).
At the primary analysis, treatment with gilteritinib did not demonstrate a statistically significant improvement in OS compared with midostaurin-based treatment. Despite missing the primary endpoint, overall survival outcomes with gilteritinib were comparable to those observed with the midostaurin-based regimen.
Safety findings were also broadly similar between the two treatment arms, with comparable rates of treatment-emergent adverse events and grade 3 or higher adverse events.
Moitreyee Chatterjee‑Kishore, Head of Oncology Development at Astellas, said the company was disappointed that the study did not reach its primary endpoint but thanked trial participants for their contributions. She noted that Astellas remains committed to advancing FLT3-targeted therapies to improve outcomes for patients with acute myeloid leukemia.
Marleen C. Breems‑de Ridder, CEO of the HOVON Foundation, emphasized that negative or neutral trial outcomes still contribute valuable scientific insights. She added that the HOVON and AMLSG research groups will continue conducting collaborative clinical studies aimed at improving treatment outcomes for patients with hematologic malignancies.
Astellas and the study investigators will continue a comprehensive evaluation of the PASHA trial data, including secondary endpoints, subgroup analyses, and the safety of gilteritinib when combined with chemotherapy. The results are expected to be further analysed and disseminated through scientific channels.
Gilteritinib is an oral FMS-like tyrosine kinase 3 (FLT3) inhibitor with activity against both FLT3-internal tandem duplication (ITD) and FLT3-tyrosine kinase domain (TKD) mutations, two important drivers of disease progression in AML. The drug was discovered through a research collaboration with Kotobuki Pharmaceutical and is currently marketed globally as Xospata.
The therapy previously demonstrated clinical benefit in the Phase 3 ADMIRAL trial (NCT02421939), which showed improved outcomes compared with salvage chemotherapy in adults with relapsed or refractory FLT3-mutated AML. Based on these results, Xospata is approved in several regions including the United States, Japan, China, and multiple European countries for patients with relapsed or refractory FLT3-positive AML.
Acute Myeloid Leukemia is an aggressive cancer of the blood and bone marrow that primarily affects older adults. Approximately one-third of patients newly diagnosed with AML harbor mutations in the FLT3 gene, which are associated with higher relapse risk and poorer survival outcomes. FLT3 mutation status may also evolve during the course of treatment, including at relapse.
Astellas stated that the PASHA study outcome is expected to have only a minor impact on the company’s financial results for the fiscal year ending March 31, 2026.
References
Astellas and Hovon Confirm Phase 3 Study Did not Meet its Primary Endpoint of Overall Survival in Patients with Newly Diagnosed FLT3m+ AML, 09 March 2026, https://newsroom.astellas.com/2026-03-09-astellas-and-hovon-confirm-phase-3-study-did-not-meet-its-primary-endpoint-of-overall-survival-in-patients-with-newly-diagnosed-flt3m-aml
A Study of Gilteritinib Versus Midostaurin in Combination with Induction and Consolidation Therapy Followed by One-year Maintenance in Patients with Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes with Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy (HOVON 156 AML), ClinicalTrials.gov ID NCT04027309, https://clinicaltrials.gov/study/NCT04027309
About the Author
Sana Jamil Khan is a B.Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.