• In a Phase 3 trial, Astellas’ Xospata improved survival for patients with relapsed or refractory acute myeloid leukemia (AML) compared to chemotherapy, according to results presented at the American Association for Cancer Research annual meeting this week.
• The median overall survival for patients who received Xospata was 9.3 months compared to 5.6 months for patients who received second-line chemotherapy.
• At one year, 37% of patients who were given Xospata, which targets a mutation called FLT3, were still alive compared to 17% of those treated with chemotherapy.

Japanese drugmaker Astellas won a Food and Drug Administration approval for Xospata (gilteritinib​) in November 2018 based on safety data from 138 patients and initial response data. Missing, however, was data demonstrating the drug’s efficacy versus chemotherapy. 

Now, confirmatory data from 371 patients in that study show Xospata is more effective than standard chemotherapy, even though most patients still didn’t survive long-term. 

AML, which develops in the bone marrow, is relatively rare, although more than 10,000 AML patients are estimated to have died from the disease in 2018

Alexander Perl, an associate professor of hematology-oncology at the University of Pennsylvania and the study’s lead author, said in a statement Xospata is currently being tested in combination with other therapies as well as a frontline therapy, with hopes of improving treatment for patients with FLT3-positive AML. 

In that latter indication, Astellas’ drug will compete with Novartis’ Rydapt (midostaurin), which was approved in 2017 to treat newly diagnosed AML patients with an FLT3 mutation.

The FLT3 mutation is found in about a third of AML patients diagnosed in the U.S., and patients with relapsed or refractory FLT3-mutated AML have a particularly poor prognosis. Standard chemotherapy has low remission rates, and remissions tend to last only for a short period of time.

“These survival data combined with gilteritinib’s relatively low toxicity establish gilteritinib monotherapy as the new standard of care for patients with relapsed or refractory FLT3-mutated AML,” Perl said in a statement from AACR. 

Of the 371 patients enrolled in the trial, 247 were randomly assigned to gilteritinib and 124 to standard chemotherapy.

Xospata was the third AML drug to get a green light from the FDA last year. Its OK followed the approval of Daurismo (glasdegib), a tablet to be used in combination with chemotherapy in adults 75 years of age or older with other chronic health conditions, and Tibsovo (ivosidenib), a targeted therapy for patients with mutations in the IDH1 gene.

Tibsovo, marketed by Agios Pharmaceuticals, was also approved based on data from relatively few patients. The drug was studied in a single-arm trial of 174 adults with relapsed or refractory AML with an IDH1 mutation.

Ned Sharpless, soon-to-be acting FDA head, told BioPharma Dive last year that the clinical trial landscape for cancer drugs is shifting dramatically. Instead of testing drugs on thousands of patients, studies of just a few hundred patients are becoming the norm as drugmakers zero in on genetically targeted therapies.

That’s particularly true in AML, as recent approvals have shown.