FDA Approves Olutasidenib for Relapsed or Refractory Acute Myeloid Leukaemia with a Susceptible IDH1 Mutation

On 1 December 2022, the US Food and Drug Administration (FDA) approved olutasidenib (Rezlidhia) capsules for adult patients with relapsed or refractory acute myeloid leukaemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.

The FDA also approved the Abbott RealTime IDH1 Assay to select patients for olutasidenib.

Approval was based on Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicentre clinical study that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the above assay. Olutasidenib was given orally,150 mg twice daily, until disease progression, unacceptable toxicity, or haematopoietic stem cell transplantation. The median treatment duration was 4.7 months (range, 0.1-26 months). Sixteen patients (11%) underwent haematopoietic stem cell transplantation following olutasidenib.

Efficacy was established on the rate of complete remission (CR) plus complete remission with partial haematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence. The CR+CRh rate was 35% (95% confidence interval [CI] 27%, 43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI 13.5 months, not reached).

Among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion independent during any 56-day post-baseline period.

The most common adverse reactions (≥20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnoea, fever, rash, mucositis, diarrhoea, and transaminitis. The prescribing information contains a Boxed Warning alerting healthcare professionals and patients about the risk of differentiation syndrome which can be fatal.

The recommended olutasidenib dose is 150 mg taken orally twice daily on an empty stomach (at least 1 hour before or 2 hours after a meal) until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months allowing for clinical response.

Full prescribing information for Rezlidhia is available here.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.