Olutasidenib
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-OLUTASIDENIB |
|---|---|
| Type | Drug |
| Aliases | RezlidhiaОлутасиденіб |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Diseases | DIS-AML |
| Sources | SRC-CIVIC SRC-ESMO-AML-2020 SRC-NCCN-AML-2025 |
Drug Facts
| Class | Selective oral mutant IDH1 (R132) inhibitor |
|---|---|
| Mechanism | Oral, potent, selective small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) bearing R132 substitutions (R132H, R132C, R132G, R132S, R132L). Binds an allosteric site on the mutant IDH1 dimer, blocking the neomorphic conversion of α-ketoglutarate to (R)-2-hydroxyglutarate (2-HG) — the oncometabolite that drives DNA + histone hypermethylation and arrests myeloid differentiation. 2-HG suppression restores myeloid differentiation in IDH1-mutant AML blasts (induces phenotypic conversion of blasts to functional neutrophils — analogous to ivosidenib mechanism, but with less potential for QTc prolongation in the head-to-head pharmacology profile). Pivotal Study 2102-HEM-101 (Cortes Blood 2024) Phase II Cohort R/R AML (n=153, IDH1-R132 mutant relapsed/refractory AML) showed CR+CRh 35%, CR 32%, mDOR 25.9 mo, median time to CR/CRh 1.9 mo, transfusion independence 56-fold among CR/C... |
| Typical dosing | 150 mg PO twice daily (every 12 hours) on an empty stomach (≥1 h before or ≥2 h after food) — high-fat meals significantly increase exposure. Continue until disease progression, transplant, unacceptable toxicity, or up to 2 years of treatment for responders with sustained CR. Monitor for differentiation syndrome (DS, formerly "IDH-DS") starting from week 1 — signs: pulmonary infiltrates, dyspnea, hypoxia, pleural / pericardial effusion, unexplained fever, bone pain, peripheral edema, hyperleukocytosis, hypotension, renal dysfunction. Treat suspected DS empirically with dexamethasone 10 mg IV q12h + supportive care; do NOT delay steroids while awaiting confirmation. Monitor LFTs (transaminit... |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-04-29 |
Warnings
- Differentiation Syndrome (BOXED WARNING): potentially fatal; can occur as early as 1 day and up to 18+ months after start. Symptoms: dyspnea, fever, lung infiltrates, hypoxia, pleural / pericardial effusion, bone pain, edema, hyperleukocytosis, hypotension, renal dysfunction. Treat empirically with dexamethasone + hemodynamic support; hold olutasidenib for severe cases until DS resolves.
Notes
Olutasidenib (Rezlidhia, Rigel Pharmaceuticals) is the second FDA-approved IDH1-mutant inhibitor (after ivosidenib / Tibsovo, Servier 2018). Both target IDH1-R132 mutations in R/R AML; key differences: (1) olutasidenib pivotal data were in R/R AML mono (Cohort R/R, n=153, ORR/CR/CRh 35%); ivosidenib has both R/R AML mono approval AND newly-diagnosed AML approval (combined with azacitidine, AGILE trial). (2) Olutasidenib has a less prominent QTc-prolongation signal than ivosidenib but a more prominent transaminitis signal. (3) Differentiation syndrome boxed warning applies to BOTH agents (class IDH-inhibitor effect — analogous to ATRA-DS in APL). (4) Cross-resistance: switching from ivosidenib → olutasidenib at progression CAN restore response in a subset (Watts Blood 2024) — suggests IDH1-R132 second-site resistance mutations may differ between agents. NCCN-AML 2025 lists olutasidenib as a category 2A option for IDH1-mut R/R AML (alongside ivosidenib). EMA has NOT approved olutasidenib (as of 2026-04-29) — in EU, ivosidenib is the IDH1-mut R/R AML standard. Companion diagnostic: Abbott RealTime IDH1 Assay (FDA-cleared); NGS panels (FoundationOne Heme, MyAML, OncoMap) detecting IDH...
Used By
Regimens
REG-OLUTASIDENIB-AML-IDH1-CONSOLIDATION- Olutasidenib monotherapy (R/R IDH1-mutant AML, post-induction consolidation/maintenance)REG-OLUTASIDENIB-AML-RR-IDH1- Olutasidenib monotherapy (Study 2102-HEM-101) — R/R AML with susceptible IDH1 mutation