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FDA expands approval of Tibsovo for IDH1-mutant acute myeloid leukemia
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The FDA expanded the approval of ivosidenib for acute myeloid leukemia.
The new indication allows the agent to be used as monotherapy for individuals aged 75 years or older with newly diagnosed AML who have isocitrate dehydrogenase-1 (IDH1) mutations as detected by an FDA-approved test or are ineligible for intensive induction chemotherapy.
Last summer, the FDA approved ivosidenib (Tibsovo, Agios Pharmaceuticals) for the treatment of adults with relapsed or refractory AML with IDH1 mutations.
“Despite several new AML medicines approved in the last 2 years, many newly diagnosed patients are still not eligible for existing therapies or combination regimens because of age and other comorbidities,” Chris Bowden, MD, chief medical officer at Agios, said in a company-issued press release. “With [this] additional Tibsovo approval, we are now able to provide a targeted, oral therapy to patients with an IDH1 mutation who may not have other treatment options.”
Ivosidenib inhibits IDH1, which is mutated in an estimated 6% to 10% of AML cases. The mutated enzyme blocks normal blood stem cell differentiation, contributing to AML genesis.
The FDA approved the new indication based on results from a phase 1 study that included 28 adults aged 75 years or older (median age, 77 years; range, 64-87) with newly diagnosed AML who had IDH1 mutations or were ineligible for intensive induction chemotherapy due to comorbidities. Those comorbidities included ECOG performance status of 2 or higher, severe cardiac or pulmonary disease, hepatic impairment with bilirubin greater than 1.5 times the upper limit of normal, or creatinine clearance less than 45 mL/min.
Two-thirds (68%) of patients had AML with myelodysplasia-related changes.
Patients received ivosidenib 500 mg daily.
The combined rate of complete remission and complete remission with partial hematologic improvement — defined as less than 5% of blasts in bone marrow, no evidence of disease and partial recovery of peripheral blood counts — served as the primary endpoint.
Results showed 28.6% of patients achieved complete remission, and 42.9% achieved either complete remission or complete remission with partial hematologic improvement.
Seven of 12 patients (58.3%) who achieved complete remission or complete remission with partial hematologic improvement remained in remission at 1 year.
Seven (25%) patients experienced differentiation syndrome, and six of them recovered.
The most common adverse reactions included diarrhea, fatigue, decreased appetite, edema, nausea, leukocytosis, arthralgia, abdominal pain, dyspnea, myalgia, constipation, differentiation syndrome, dizziness, prolonged QT interval, mucositis and vomiting.
“The phase 1 results for Tibsovo demonstrated that this oral, single-agent therapy can induce durable responses in newly diagnosed [patients with] AML with an IDH1 mutation,” Gail J. Roboz, MD, professor of medicine, director of the leukemia program and member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, said in the release. “Many patients included in the study had features associated with particularly aggressive and challenging forms of AML, including secondary disease, adverse risk genetics and prior treatment with hypomethylating agents.”
Phase 3 trials are underway to evaluate ivosidenib in combination with intensive chemotherapy and azacitidine for treatment of newly diagnosed AML.