The Food and Drug Administration (FDA) has approved Rezlidhia™ (olutasidenib) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.
Olutasidenib is a small-molecule inhibitor of mutated IDH1. By inhibiting mutant IDH1, olutasidenib reduces 2-hydroxyglutarate levels and restores normal cellular differentiation of myeloid cells.
The approval was based on data from an open-label, single-arm clinical trial (ClinicalTrials.gov Identifier: NCT0271957) that included 147 patients with relapsed or refractory AML with an IDH1 mutation confirmed through testing. Olutasidenib was administered orally at a dose of 150mg twice daily until disease progression, development of unacceptable toxicity, or hematopoietic stem cell transplantation.
The primary endpoint of the study was a composite of a complete remission (CR) plus a complete remission with partial hematological recovery (CRh). Efficacy was also measured by the duration of CR+CRh, as well as the rate of conversion from transfusion dependence to transfusion independence.
Results showed a CR+CRh rate of 35% (95% CI, 27-43) with a median duration of CR+CRh of 25.9 months (95% CI, 13.5, not reached). Of the patients who achieved a CR or CRh, the median time to CR or CRh was 1.9 months (range, 0.9-5.6 months).
Among patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline (n=86), 34% became transfusion independent during any 56-day post-baseline period. Among the 61 patients who were independent of both RBC and platelet transfusions at baseline, 64% remained transfusion independent during any 56-day post-baseline period.
As for safety, the most common adverse reactions reported with treatment were nausea, fatigue/malaise, arthralgia, constipation, dyspnea, pyrexia, rash, mucositis, diarrhea and transaminitis. Laboratory abnormalities included increased aspartate aminotransferase, increased alanine aminotransferase, decreased potassium, decreased sodium, increased alkaline phosphatase, increased creatinine, increased lymphocytes, increased bilirubin, leukocytosis, increased uric acid, and increased lipase. The prescribing information contains a Boxed Warning regarding the risk of differentiation syndrome, which can be fatal.
Commenting on the approval, Jorge E. Cortes, MD, Director, Georgia Cancer Center, Cecil F. Whitaker Jr, GRA Eminent Scholar Chair in Cancer, and phase 2 trial investigator, said: “Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, Rezlidhia may provide an effective, new treatment option with a well characterized safety profile.”
Rezlidhia is supplied as 150mg capsules. Patients should be selected for treatment based on the presence of IDH1 mutations in blood or bone marrow. The FDA has approved the Abbott RealTime IDH1 Assay to select patients for olutasidenib.
- Rigel announces US FDA approval of Rezlidhia™ (olutasidenib) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation. News release. December 1, 2022. https://www.prnewswire.com/news-releases/rigel-announces-us-fda-approval-of-rezlidhia-olutasidenib-for-the-treatment-of-adult-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-with-a-susceptible-idh1-mutation-301692086.html.
- Rezlidhia. Package insert. Rigel Pharmaceuticals; 2022. Accessed December 2, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215814s000lbl.pdf.