FDA News

FDA approves Tibsovo for IDH1-mutated acute myeloid leukemia

The FDA approved ivosidenib for the treatment of adults with relapsed or refractory acute myeloid leukemia who harbor IDH1 mutations detected by an FDA-approved test.

Ivosidenib (Tibsovo, Agios Pharmaceuticals) — an oral targeted inhibitor of the IDH1 enzyme — is the only FDA-approved therapy for this patient population.

“The FDA approval of Tibsovo — our first wholly owned drug and the second approved medicine from our research platform in less than a year — is an incredibly exciting milestone for our company and, importantly, for the approximately 6% to 10% of AML patients with an IDH1 mutation who have been waiting for new treatment options that work radically different than conventional chemotherapy,” David Schenkein, MD, CEO at Agios, said in a company-issued press release.

The FDA based the approval on results of an open-label, single-arm, multicenter phase 1 study that included 174 adults (median age, 67 years; range, 18-87) with relapsed or refractory AML with IDH1 mutations identified or confirmed by the Abbott RealTime IDH1 assay (Abbott), which received FDA approval concurrently with ivosidenib.

Trial participants had received a median two prior anticancer therapies (range, 1-6), more than half (63%) were refractory to their previous therapy, and 33% had secondary AML.

Patients received ivosidenib at starting doses of 500 mg daily. Treatment continued until disease progression, unacceptable toxicity or receipt of hematopoietic stem cell transplantation.

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.

Fifty-seven (32.8%) patients achieved complete remission or complete remission with partial hematologic improvement. This included 43 (24.7%) patients with complete remission and 14 (8%) who achieved complete remission with partial hematologic improvement.

Median duration of these remissions was 8.2 months (95% CI, 5.6-12), and median time to best response was 2 months (range, 0.9-5.6).

Forty-one (37.3%) of the 110 patients who were dependent on red blood cell and/or platelet transfusions at baseline became transfusion independent during any 56-day postbaseline period.

Thirty-eight of 64 (59.4%) patients who were independent of red blood cell and platelet transfusions at baseline remained transfusion independent during any 56-day postbaseline period.

Twenty-one (12%) of 174 patients underwent stem cell transplant after ivosidenib treatment.

A safety analysis included 179 patients (median duration of exposure, 3.9 months; range, 0.1-39.5).

Thirty-four (19%) patients experienced differentiation syndrome.

The most common adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, prolonged QT interval, rash, pyrexia, cough and constipation.

Hagop Kantarjian, MD
Hagop M. Kantarjian

The most frequent serious adverse reactions included differentiation syndrome (10%), leukocytosis (10%) and prolonged QT interval (7%).

“AML patients who relapse or are refractory to available therapies have few, if any, treatment options,” Hagop M. Kantarjian, MD, professor and chair of the department of leukemia at The University of Texas MD Anderson Cancer Center, said in the release. “The clinical study demonstrated that Tibsovo has the potential to deliver strong, durable responses as a single agent and can help patients achieve and maintain transfusion independence. IDH inhibitors represent a new class of noncytotoxic, targeted therapies for AML patients with IDH mutations.”

The FDA approved ivosidenib for the treatment of adults with relapsed or refractory acute myeloid leukemia who harbor IDH1 mutations detected by an FDA-approved test.

Ivosidenib (Tibsovo, Agios Pharmaceuticals) — an oral targeted inhibitor of the IDH1 enzyme — is the only FDA-approved therapy for this patient population.

“The FDA approval of Tibsovo — our first wholly owned drug and the second approved medicine from our research platform in less than a year — is an incredibly exciting milestone for our company and, importantly, for the approximately 6% to 10% of AML patients with an IDH1 mutation who have been waiting for new treatment options that work radically different than conventional chemotherapy,” David Schenkein, MD, CEO at Agios, said in a company-issued press release.

The FDA based the approval on results of an open-label, single-arm, multicenter phase 1 study that included 174 adults (median age, 67 years; range, 18-87) with relapsed or refractory AML with IDH1 mutations identified or confirmed by the Abbott RealTime IDH1 assay (Abbott), which received FDA approval concurrently with ivosidenib.

Trial participants had received a median two prior anticancer therapies (range, 1-6), more than half (63%) were refractory to their previous therapy, and 33% had secondary AML.

Patients received ivosidenib at starting doses of 500 mg daily. Treatment continued until disease progression, unacceptable toxicity or receipt of hematopoietic stem cell transplantation.

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.

Fifty-seven (32.8%) patients achieved complete remission or complete remission with partial hematologic improvement. This included 43 (24.7%) patients with complete remission and 14 (8%) who achieved complete remission with partial hematologic improvement.

Median duration of these remissions was 8.2 months (95% CI, 5.6-12), and median time to best response was 2 months (range, 0.9-5.6).

Forty-one (37.3%) of the 110 patients who were dependent on red blood cell and/or platelet transfusions at baseline became transfusion independent during any 56-day postbaseline period.

Thirty-eight of 64 (59.4%) patients who were independent of red blood cell and platelet transfusions at baseline remained transfusion independent during any 56-day postbaseline period.

Twenty-one (12%) of 174 patients underwent stem cell transplant after ivosidenib treatment.

A safety analysis included 179 patients (median duration of exposure, 3.9 months; range, 0.1-39.5).

Thirty-four (19%) patients experienced differentiation syndrome.

The most common adverse reactions included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, prolonged QT interval, rash, pyrexia, cough and constipation.

Hagop Kantarjian, MD
Hagop M. Kantarjian

The most frequent serious adverse reactions included differentiation syndrome (10%), leukocytosis (10%) and prolonged QT interval (7%).

“AML patients who relapse or are refractory to available therapies have few, if any, treatment options,” Hagop M. Kantarjian, MD, professor and chair of the department of leukemia at The University of Texas MD Anderson Cancer Center, said in the release. “The clinical study demonstrated that Tibsovo has the potential to deliver strong, durable responses as a single agent and can help patients achieve and maintain transfusion independence. IDH inhibitors represent a new class of noncytotoxic, targeted therapies for AML patients with IDH mutations.”