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TIBSOVO (ivosidenib tablets) is the only targeted therapy that was studied in a phase 3 trial specifically designed for newly diagnosed patients with mIDH1 AML1

TIBSOVO + azacitidine was studied in a global, phase 3, multicenter, randomized, double-blind, placebo-controlled trial in an IC-ineligible patient population reflective of that seen in clinical practice.1,2

AGILE study design

AGILE study design1,3

agile-study-design-outlined Chart agile-study-design-mobile-outlined Chart
  • Efficacy was established on the basis of event-free survival (EFS), overall survival (OS), and rate and duration of complete remission (CR)1,a,b
  • Treatment failure was defined as failure to achieve CR by Week 24. Patients who achieved CRh but not CR did not meet the EFS definition of treatment success1,c
aCR was defined as <5% blasts in the bone marrow and no Auer rods, absence of extramedullary disease, full recovery of peripheral blood counts (absolute neutrophil count ≥1000/μL and platelets ≥100,000/μL), and independence of red blood cell transfusions.1,3
bEFS was defined as time from randomization until treatment failure (ie, failure to achieve CR by Week 24), relapse from remission, or death from any cause, whichever occurred first.1
cCRh was defined as <5% blasts in the bone marrow and no Auer rods, absence of extramedullary disease, and partial recovery of peripheral blood counts (absolute neutrophil count >500/μL and platelets >50,000/μL).1,3
The trial was initially powered for 200 participants. However, the Independent Data Monitoring Committee suggested halting enrollment after 146 patients when a clinically important difference between the two treatment groups was achieved.1,3

AML, acute myeloid leukemia; CRh, complete remission with partial hematologic recovery; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EORTC QLC-C30, European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EQ-5D-FL, 5-level EuroQol Five Dimensions Questionnaire (descriptive system and visual analogue scale); HMA, hypomethylating agent; IV, intravenous; LVEF, left ventricular ejection fraction; mIDH1, mutated isocitrate dehydrogenase-1; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; ORR, objective response rate; QD, once a day; SC, subcutaneous.

See baseline characteristics

Baseline patient demographics and disease characteristics1

  TIBSOVO® (500 mg daily)
+ azacitidine (n=72)		 Placebo + azacitidine
(n=74)
Median age, years (min, max) 76 (58, 84) 76 (45, 94)
Age categories, n (%)
<65 years 4 (6) 4 (5)
≥65 years to <75 years 29 (40) 27 (36)
≥75 years 39 (54) 43 (58)
Cytogenetic risk status,a n (%)
Favorable 3 (4) 7 (9)
Intermediate 48 (67) 44 (59)
Poor 16 (22) 20 (27)
Other 3 (4) 1 (1)
Missing 2 (3) 2 (3)
ECOG PS, n (%)
0 14 (19) 10 (14)
1 32 (44) 40 (54)
2 26 (36) 24 (32)
Transfusion dependent at baseline,b n (%) 39 (54) 40 (54)
Type of AML, n (%)
De novo AML 54 (75) 53 (72)
Secondary AML 18 (25) 21 (28)
Therapy-related AML 2 (3) 1 (1)
MDS related 10 (14) 12 (16)
MPN related 4 (6) 8 (11)

aCytogenic risk status: Investigators used the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).1

bPatients were defined as transfusion dependent at baseline if they received any RBC or platelet transfusion within 56 days prior to the first dose of study treatment.1

AML, acute myeloid leukemia; ECOG PS, Eastern Cooperative Oncology Group Performance Status; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; NCCN, National Comprehensive Cancer Network®; RBC, red blood cell.

AML, acute myeloid leukemia; IC, induction chemotherapy; mIDH1, mutant isocitrate dehydrogenase‑1.

TIBSOVO + azacitidine is proven to significantly increase overall survival (OS)1

More than threefold improvement in mOS with TIBSOVO + AZA vs placebo + AZA1,4

TIBSOVO + azacitidine vs placebo + azacitidine overall survival graph. TIBSOVO + azacitidine vs placebo + azacitidine overall survival graph.

Description

Kaplan-Meier curve presenting overall survival data from two analyses — a primary OS analysis and a long-term follow-up OS analysis — comparing TIBSOVO plus azacitidine (AZA) versus placebo plus AZA in patients with IDH1-mutated acute myeloid leukemia (AML).

In the primary OS analysis, the survival curves separate over time in favor of TIBSOVO + AZA. Median overall survival was 24.0 months with TIBSOVO + AZA (95% CI, 11.3–34.1) compared with 7.9 months with placebo + AZA (95% CI, 4.1–11.3). The hazard ratio was 0.44 (P=0.0010).

In the long-term follow-up OS analysis, median overall survival was 29.3 months with TIBSOVO + AZA (95% CI, 13.2–NR) compared with 7.9 months with placebo + AZA (95% CI, 4.1–11.3). The hazard ratio was 0.42 (P<0.0001). The survival curves maintain separation through approximately 50 months of follow-up.

Improvements in OS were seen in patients on TIBSOVO + AZA regardless of baseline status, including de novo status, region, age, baseline ECOG PS score, sex, race, baseline cytogenetic risk status, WHO classification of AML, baseline white blood cell count, and baseline percentage of bone marrow blasts.5

Primary OS analysis

24.0 months mOS with TIBSOVO + azacitidine (95% CI, 11.3–34.1) vs 7.9 months with azacitidine alone (95% CI, 4.1–11.3)1,a

  • 56% reduction in risk of death (HR, 0.44 [95% CI, 0.27–0.73]; P=0.0010)1
  • The percentage of OS events at the time of analysis was 39% (n=28) and 62% (n=46) in the TIBSOVO + azacitidine and placebo + azacitidine arms, respectively1

aIn the primary analysis from the AGILE study, 146 patients were 1:1 randomized: 72 to TIBSOVO + AZA and 74 to PBO + AZA.1,3 The data cutoff date of the primary analysis from the AGILE study was March 2021 with a median follow-up of 15.1 months for the OS analysis.

bIn the long-term follow-up analysis from the AGILE study, 148 patients were 1:1 randomized: 73 to TIBSOVO + AZA and 75 to PBO + AZA.2,4 The data cutoff date of the long-term follow-up analysis from the AGILE study was June 2022 with a median follow-up of 28.6 months for the OS analysis.

For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response1

Overall survival benefit with TIBSOVO + azacitidine increased over time compared to placebo + AZA

Greater than 3X increase in OS rates at 24 and 36 months with TIBSOVO + azacitidine3

Greater Than Three Times Increase in Overall Survival Chart. Greater Than Three Times Increase in Overall Survival Chart. Greater Than Three Times Increase in Overall Survival Chart.
Chart Legend: TIBSOVO + AZA and Placebo + AZA
Greater Than Three Times Increase in Overall Survival Chart. Greater Than Three Times Increase in Overall Survival Chart. Greater Than Three Times Increase in Overall Survival Chart.

Description

Bar chart presenting overall survival rates at 12, 24, and 36 months in patients treated with TIBSOVO plus azacitidine (AZA) versus placebo plus AZA.

At 12 months, the overall survival rate was 63% with TIBSOVO + AZA compared with 38% with placebo + AZA.

At 24 months, the overall survival rate was 53% with TIBSOVO + AZA compared with 17% with placebo + AZA.

At 36 months, the overall survival rate was 41% with TIBSOVO + AZA compared with 12% with placebo + AZA.

AML, acute myeloid leukemia; AZ, azacitidine; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; IDH1, isocitrate dehydrogenase‑1; mOS, median overall survival; PBO, placebo; WHO, World Health Organization.

TIBSOVO + azacitidine demonstrated rapid and durable remissions2

TIBSOVO + azacitidine demonstrated significantly higher rates of CR and CR+CRh compared with azacitidine (P<0.0001)1,c

TIBSOVO-azacitidine-combo Chart TIBSOVO-azacitidine-combo-mobile Chart

Description

Graphic presenting complete remission (CR) and composite remission (CR+CRh) rates in patients treated with TIBSOVO plus azacitidine versus placebo plus azacitidine.

With TIBSOVO plus azacitidine, the CR rate was 47% (95% CI, 35–59) and the CR+CRh rate was 51% (95% CI, 39–63).

With placebo plus azacitidine, the CR rate was 15% (95% CI, 8–25) and the CR+CRh rate was 18% (95% CI, 10–28).

  • Median duration of CR was not estimable (NE) as of the data cutoff date in the TIBSOVO + azacitidine arm (95% CI,13.0-NE) and was 11.2 months in the azacitidine arm (95% CI, 3.2-NE)1
  • Of the patients who achieved CR with TIBSOVO + azacitidine2,3
    • 88% remained in remission at 12 months (95% CI, 67.5-96.2)d
    • 59% remained in remission at 24 months (95% CI, 17.7-85.1)d
  • ​​38% of patients receiving TIBSOVO + azacitidine achieved CR by Week 24 compared with 11% of patients in the placebo + azacitidine arm2

Patients on TIBSOVO + AZA achieved higher rates of MRD negativity

30% of patients were MRD-negative by Cycle 14 in the AGILE trial4,e,f

  • All patients on TIBSOVO + AZA who achieved MRD-negativity also achieved CR

Median time to response with TIBSOVO + azacitidine2

  • First response (CR, CRi, CRp, PR, or MLFS): 2.1 months (range, 1.7‑7.5)
  • CR: 4.3 months (range, 1.7‑9.2)
  • CR+CRh: 4.0 months (range, 1.7‑8.6)

cCR was defined as <5% blasts in the bone marrow and no Auer rods, absence of extramedullary disease, full recovery of peripheral blood counts (absolute neutrophil count ≥1000/μL and platelets ≥100,000/μL), and independence of red blood cell transfusions.5 CRh was defined as <5% blasts in the bone marrow and no Auer rods, absence of extramedullary disease, and partial recovery of peripheral blood counts (absolute neutrophil count >500/μL and platelets ≥50,000/μL).1,3

dPer Kaplan-Meier estimation.3

ePatients who achieved MRD-negativity with PBO + AZA were excluded from further analysis due to small patient numbers.4

fMRD analysis was performed with a 26-gene NGS panel, including IDH1, FLT3, and NPM1.4

CR, complete remission; CRh, complete remission with partial hematologic recovery; CRi, complete remission with incomplete hematologic recovery; CRp, complete remission with incomplete platelet recovery; MLFS, morphologic leukemia-free state; PR, partial remission.

TIBSOVO + azacitidine resulted in rapid neutrophil recovery and reduction in bone marrow blasts7,g-i

Change in median ANC from baseline chart Change in median ANC from baseline chart

gBL denotes baseline, defined as a median ANC value of 0.2 x 109/L for the TIBSOVO + AZA arm and placebo + AZA arm; CxDy indicates Cycle x Day y.7

hShading denotes neutropenia and severe neutropenia, defined as ANC values of <1.0 x 109/L and <0.5 x 109/L, respectively.7

iMedian values are presented to avoid the potential masking influence of outliers resulting from differentiation of leukocytosis, which may be possible with reporting the mean values.7

The graph shows the change in median absolute neutrophil count from baseline over time in patients treated with TIBSOVO plus azacitidine versus placebo plus azacitidine. Median ANC increased early with TIBSOVO plus azacitidine and generally remained above the neutropenia threshold throughout follow-up. In the placebo plus azacitidine arm, median ANC remained lower during the earlier cycles before increasing over time.

Significant improvements in event-free survival (EFS)1,j

Treatment with TIBSOVO + azacitidine resulted in significant improvements in EFS compared with azacitidine

Endpoint TIBSOVO + azacitidine
(n=72)		 Placebo + azacitidine
(n=74)
EFS, events (%) 47 (65) 62 (84)
Treatment failure 43 (60) 59 (80)
Relapse 3 (4) 2 (3)
Death 1 (1) 1 (1)
Hazard ratiok (95% CI) 0.35 (0.17-0.72)
p valuel 0.0038

jEFS was defined as time from randomization until treatment failure (ie, failure to achieve CR by Week 24), relapse from remission, or death from any cause, whichever occurred first.1

kHazard ratio was estimated using a Cox proportional hazards model stratified by the randomization stratification factors (AML status and geographic region) with placebo + azacitidine as the denominator.

lTwo-sided P value boundary for EFS is 0.0095 and was calculated from the log-rank test stratified by the randomization stratification factors (AML status and geographic region).

TIBSOVO + azacitidine demonstrated higher EFS rates compared to azacitidine alone5

efs-12-month Chart
efs-18-month Chart

Description

Bar charts presenting event-free survival (EFS) rates at 12 months and 18 months in patients treated with TIBSOVO plus azacitidine versus placebo plus azacitidine.

At 12 months, the EFS rate was 37.4% (95% CI, 25.9–48.9) with TIBSOVO plus azacitidine compared with 12.2% (95% CI, 4.3–24.4) with placebo plus azacitidine.

At 18 months, the EFS rate was 33.3% (95% CI, 20.9–46.2) with TIBSOVO plus azacitidine compared with 6.1% (95% CI, 0.7–20.9) with placebo plus azacitidine.

AML, acute myeloid leukemia; CI, confidence interval; CR, complete remission.

More than half of patients achieved transfusion independence with TIBSOVO + azacitidine

Transfusion independence among patients who were transfusion dependent at baseline3,m,n

transfusion-independence-at-baseline-chart Chart transfusion-independence-at-baseline-chart Chart

Description

Horizontal bar chart presenting transfusion independence among patients who were transfusion dependent at baseline, comparing TIBSOVO plus azacitidine versus placebo plus azacitidine.

The transfusion independence rate was 54% with TIBSOVO plus azacitidine compared with 17% with placebo plus azacitidine (P=0.0004).

Postbaseline RBC and platelet transfusion independence regardless of baseline transfusion status2,n

postbaseline-transfusion-independence-chart Chart postbaseline-transfusion-independence-chart Chart

Description

Horizontal bar chart presenting postbaseline red blood cell (RBC) and platelet transfusion independence regardless of baseline transfusion status, comparing TIBSOVO plus azacitidine versus azacitidine alone.

The transfusion independence rate was 63% with TIBSOVO plus azacitidine compared with 51% with azacitidine alone (2-sided P=0.21).

mPostbaseline transfusion independence is defined as a period of ≥56 days with no transfusion after the start of study treatment and on or before the end of study treatment + 28 days, disease progression, confirmed relapse, death, or data cutoff date, whichever was earlier.6

nThe 95% confidence interval in the transfusion independence analysis was 37.2–69.9 for the TIBSOVO + azacitidine arm and 7.2–32.1 for the placebo + azacitidine arm.4

RBC, red blood cell.

NCCN Guidelines® recommends ivosidenib (TIBSOVO) + azacitidine as a category 1 preferred treatment option for newly diagnosed patients

≥18 years of age with mIDH1 AML who are not candidates for intensive remission induction therapy8

Real-world outcomes in TIBSOVO + azacitidine

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2023. 2. Montesinos P, Récher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519-1531. doi:10.1056/NEJMoa2117344 3. de Botton S, Montesinos P, Vives Polo S, et al. Updated efficacy and safety data from the AGILE study in patients with newly-diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine. Poster presented at: 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, IL. 4. Montesinos P, Marchione DM, Récher C, et al. Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML. Blood Adv. 2025. doi:10.1182/bloodadvances.2025016399 5. Data on file. Servier Pharmaceuticals LLC. 6. Agios Pharmaceuticals, Inc. AG120-C-009 Clinical Study Report: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination with Azacitidine in Subjects ≥18 Years of Age with Previously Untreated Acute Myeloid Leukemia with an IDH1 Mutation. 2022. 7. Fathi AT, Douglas Smith B, Anagnillo A, et al. Time to resolution of myelosuppression and associated hospitalization in patients with newly diagnosed acute myeloid leukemia treated with ivosidenib+azacitidine compared with azacitidine+placebo. Poster presented at: Eleventh Annual Meeting of the Society of Hematologic Oncology (SOHO 2023); September 6-9, 2023; Houston, TX. Poster AML-446. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed July 21, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

 

Indications

TIBSOVO is indicated for patients with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test with:

Newly Diagnosed Acute Myeloid Leukemia (AML)

  • In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy

Relapsed or Refractory AML

  • For the treatment of adult patients with relapsed or refractory AML

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML
Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome in AML: Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome can develop in patients treated with TIBSOVO. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions including laboratory abnormalities (≥25%) in patients with AML are leukocytes decreased, diarrhea, hemoglobin decreased, platelets decreased, glucose increased, fatigue, alkaline phosphatase increased, edema, potassium decreased, nausea, vomiting, phosphate decreased, decreased appetite, sodium decreased, leukocytosis, magnesium decreased, aspartate aminotransferase increased, arthralgia, dyspnea, uric acid increased, abdominal pain, creatinine increased, mucositis, rash, electrocardiogram QT prolonged, differentiation syndrome, calcium decreased, neutrophils decreased, and myalgia.

DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Advise women not to breastfeed.

Please see Full Prescribing Information, including BOXED WARNING for AML patients.

Last update: September 2026

Information on this website is reviewed through established medical, legal, and regulatory processes to support accurate, balanced, and label‑consistent communication about TIBSOVO.

 

INDICATIONS

TIBSOVO is indicated for patients with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test with:

Newly Diagnosed Acute Myeloid Leukemia (AML)

  • In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy
Indications & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.