Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced that the U.S. Food and Drug Administration (FDA) has approved REZLIDHIA™ (olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test....The FDA approval was supported by data from the open-label Phase 2 registrational study evaluating REZLIDHIA monotherapy at a dose of 150 mg twice daily in 153 mIDH1 R/R AML patients.

Targeted therapy for AML with IDH1 mutation, regimen added: Olutasidenib

This descriptive analysis suggests that olutasidenib alone or in combination with azacitidine induce complete remissions in patients with mIDH1 AML or MDS that is R/R to VEN, IVO or even HSCT.

This descriptive analysis suggests that olutasidenib alone or in combination with azacitidine induce complete remissions in patients with mIDH1 AML or MDS that is R/R to VEN, IVO or even HSCT.

We evaluated the efficacy and safety of olutasidenib in a subset of 17 patients from the Phase 2 trial (NCT02719574) previously treated with VEN combination regimens....The best response to olutasidenib was CR/CRh in 5/17 (29.4%), of which 4 (23.5%) were CR….Olutasidenib induced durable remissions in patients with mIDH1 R/R AML, including those failing prior treatment with a venetoclax-based regimen.

Olutasidenib induced durable remissions in patients with mIDH1 R/R AML, including those failing prior treatment with a venetoclax-based regimen.

Overall, olutasidenib induced durable remissions and transfusion independence with a well-characterized and manageable side-effect profile. The observed efficacy represents a therapeutic advance in this molecularly defined, poor-prognosis patient population with mIDH1 R/R AML.

Olutasidenib, with or without azacitidine, was well tolerated and showed meaningful clinical activity in patients with IDH1-mutated acute myeloid leukaemia. The results of this phase 1 study provide rationale for the continued evaluation of olutasidenib in multiple patient populations with myeloid malignancies.

Olutasidenib, with or without azacitidine, was well tolerated and showed meaningful clinical activity in patients with IDH1-mutated acute myeloid leukaemia. The results of this phase 1 study provide rationale for the continued evaluation of olutasidenib in multiple patient populations with myeloid malignancies.

Enasidenib significantly improved the response rates in patients with mIDH-2 AML....Ivosedanib significantly improved the response rates and survival rates in patients with mIDH-1 AML. Olutasidenib was also effective in patients with R/R mIDH-1 AML. More randomized double-blind multicenter clinical trials are needed to confirm these results.

...we present results of an ongoing phase 2 trial (NCT02719574) in pts receiving olutasidenib (150 mg twice daily) in combination with AZA (75 mg/m2) (Olu-AZA)….Olutasidenib in combination with AZA was well tolerated and induced durable CR/CRh in a subset of high-risk pts with mIDH1 AML.

ORR was 46% and median duration of ORR was 11.7 months...In CR+CRh responders, median OS was NR and the estimated 18-mo OS was 87%...Olutasidenib was well tolerated and induced durable CR in a subset of high-risk R/R mIDH1 AML pts. TI was achieved in all response groups. Clinical benefit, per DOR and OS, extended beyond CR+CRh responders.

Olutasidenib was well tolerated and induced durable CR in a subset of high-risk R/R mIDH1 AML pts. TI was achieved in all response groups. Clinical benefit, per DOR and OS, extended beyond CR+CRh responders.

Olutasidenib demonstrated a favorable tolerability profile as a monotherapy in patients with IDH1m relapsed/refractory acute myeloid leukemia (R/R AML), and achieved a composite complete remission (CR+CRh, or complete remission plus complete remission with partial hematologic recovery) rate of 33.3% (30% CR and 3% CRh), the primary efficacy endpoint.

SA and COMBO olutasidenib has shown favorable safety and clinical activity in IDH1m R/R AML with a SA ORR of 41% (95% CI: 21, 64) and a COMBO ORR of 46% (27, 67), and durable disease control. Olutasidenib induces deep responses with IDH1 mutation clearance in a subset of treated pts.