The European Commission has approved Astellas Pharma‘s small molecule inhibitor Xospata (gilteritinib) for the treatment of relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, the company has announced.
The approval makes Xospata available across all member countries of the European Union (EU), as well as Iceland, Norway, and Liechtenstein, and follows last year’s approvals by the U.S. and Japanese regulatory authorities for the same indication.
“Today’s approval marks a significant advance for patients living with relapsed or refractory, FLT3 mutation-positive acute myeloid leukemia,” Andrew Krivoshik, MD, PhD, senior vice president, and global therapeutic area head of oncology development at Astellas, said in a news release.
“We look forward to working with health authorities across the EU to bring [Xospata] gilteritinib to patients who need it the most, as soon as possible,” he added.
FLT3 is a protein that helps regulate the survival and proliferation of blood stem cells. This protein normally gets activated when it interacts with another protein, but some mutations in the FLT3 gene create a protein that is constantly active, encouraging the growth of abnormal leukemia cells.
About 30% of AML patients carry an activating mutation in the FLT3 gene, and they have a more severe form of the cancer with a worse prognosis.
While many FLT3 inhibitors exist for these patients — the approved Rydapt (midostaurin), quizartinib (in development), and sorafenib (off-label use) — they have failed to induce complete remission, are associated with toxicity, and have a short-lasting efficacy due to the emergence of resistance mutations in FLT3, namely one in the tyrosine kinase domain (TKD).
Xospata, however, targets this TKD resistance mutation in addition to the internal tandem duplication (ITD), two important mutations in the FLT3 gene. This makes Xospata a better approach for FLT3-mutated AML, researchers say.
Its approval was based on data from the ADMIRAL Phase 3 trial (NCT02421939), an open-label, multicenter, randomized study that compared the efficacy of Xospata to that of chemotherapy in adults with AML bearing an FLT3 mutation, and whose cancer had progressed or returned after first-line therapy.
The study recruited 371 participants, 39% of whom had failed to respond to first-line therapy and 61% who responded but eventually saw their disease progress again. One-third received chemotherapy and two-thirds received oral Xospata treatment once a day.
Participants in the Xospata group survived significantly longer than those in the chemotherapy group — a median of 9.3 months versus 5.6 months — representing a 36% reduction in the risk of death. After one year, 37% of patients on Xospata were alive, compared with 17% of those on chemotherapy.
Response rates were also better, with 21.1% of patients on Xospata achieving a complete response (total cancer eradication), versus 10.5% of those on chemo.
Adverse events were similar in both groups and included low levels of neutrophils (a type of immune cell), anemia (low red blood cell count), fever, and low platelet count. Fewer patients had severe adverse events in the Xospata group than in the chemotherapy group.
“AML is a rare cancer, and patients with an FLT3 mutation have a particularly poor prognosis, with a median survival of less than six months following treatment with salvage chemotherapy,” said Giovanni Martinelli, MD, an investigator in the ADMIRAL trial. “Gilteritinib is a new and clinically meaningful treatment option that provides a welcome advance for patients and healthcare professionals across the European Union.”
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