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TIBSOVO is the first and only FDA-approved therapy to target mIDH1 in R/R MDS1,2

TIBSOVO was evaluated in adult patients with R/R mIDH1 MDS in an open-label, single-arm, multicenter study.1

Study design Baseline characteristics

mIDH1, mutated isocitrate dehydrogenase-1; R/R, relapsed or refractory.

TIBSOVO demonstrated deep and durable remissions1,3

39%

of patients achieved complete remission with TIBSOVO (95% CI, 17.3-64.3)1,a
  • Rapid remissions: median time to CR was 1.9 months (range, 1.0-5.6)1

Durability of remissions with TIBSOVO

  • Median duration of CR was not reached by data cutoff (range, 1.9-80.8+ months; 95% CI, 1.9-NE)1,3,b
  • 69% of patients who achieved CR remained in remission at 12 months3,c
  • 43% percent of patients who achieved CR remained in remission for more than 5 years3,c
Treatment duration and best overall response (N=18)3
Treatment Duration of TIBSOVO® Graph HMA, INV HMA HMA IC HMA HMA HMA HMA HMA HMA HMA IC HMA HMA HMA, Other HMA, INV HMA IC Treatment duration (months) 12 24 36 48 60 Patients (based on PT) 72 6 18 30 42 54 66 78 84 0 Best Response CR mCR SD PD HI for non-CR/PR subjects CR+PR response Disease progression/relapse Death Progression to AML HCT

Patients treated with TIBSOVO achieved hematologic improvements, including rapid neutrophil recovery3

  • Rapid neutrophil recovery was seen in all patients with CR and more than half of patients (4/7) who did not achieve CR (57%)
    • Median time to neutrophil recovery was 0.97 months
  • Of the 8 patients that experienced marrow CR, 50% experienced hematologic improvements in ≥1 lineage including RBC, platelet, and/or neutrophild
  • One (6%) patient went on to receive stem cell transplantation following treatment with TIBSOVO

aCR was defined as bone marrow ≤5% myeloblasts with normal maturation of all cell lines, hemoglobin ≥11 g/dL, platelets ≥100 x 109/L, neutrophils ≥1.0 x 109/L, and response lasting at least 4 weeks.3 43% of CR responders had baseline bone marrow blasts <5%.1

bDOCR was derived based on Kaplan-Meier method and is the date of the first documented CR (lasting ≥4 weeks) to the date of the first documented relapse or death, whichever was earlier.1 Plus sign (+) indicates a censored observation.

cPer Kaplan-Meier estimation.3

d Of those experiencing hematologic improvements in >1 lineage, 25% (2/8) had improved erythrocyte counts, 25% (2/8) had improved platelet counts, and 50% (4/8) had improved neutrophil counts.3

DOCR, duration of CR; HCT, hematopoietic stem cell transplantation; HMA, hypomethylating agent; IC, intensive chemotherapy, INV, investigational agent; mCR, marrow CR; NE, not estimable; PD, progressive disease; PR, partial remission; PT, prior therapy; SD, stable disease.

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

Majority of patients achieved or maintained transfusion independence with TIBSOVO1,e

Median time to transfusion independence was 2.43 months in patients who were transfusion-dependent at baseline.3

78%
78% of patients (7/9) who were transfusion-independent at baseline maintained transfusion independence.1
  • 100% of patients who were platelet transfusion-independent at baseline maintained transfusion independence3

Duration of transfusion independence with TIBSOVO3

  • 67% of patients (4/6) who were baseline transfusion dependent and achieved transfusion independence had a duration of transfusion independence >4 months, with the longest lasting 272+ days and maintained through the end of treatment
  • Of the 72% of patients who achieved or maintained transfusion independence, median duration of transfusion independence was not reached but ranged between 1.9 and 78.8 monthse,f

ePostbaseline transfusion independence was defined as a period of ≥56 days with no red blood cell and/or platelet transfusions after the start of study treatment and on or before the end of study treatment.

fNine observations were censored.

Overall survival with TIBSOVO3

Median OS was estimated to be 35.7 months3

0 0 . 0 0.2 0.1 0.5 0.4 0.3 0 . 7 0.6 1 . 0 0.9 0.8 8 16 24 32 40 Overall survival (months) Kaplan-Meier estimate 48 56 64 72 80 84 4 12 20 28 36 44 52 60 68 76 2 10 18 26 34 42 50 58 66 74 82 6 14 22 30 38 46 54 62 70 78 90 86 92 88 Number of patients at risk 18 12 10 7 5 4 4 4 4 4 2 17 12 8 5 4 4 4 4 4 3 18 12 10 6 5 4 4 4 4 3 1 1 1 1 0 16 11 8 5 4 4 4 4 4 3 Median OS (95% CI, 13.1-NE) 35.7 months 0 0 . 0 0.2 0.1 0.5 0.4 0.3 0 . 7 0.6 0.9 0.8 8 16 24 32 40 Overall survival (months) Kaplan-Meier e stim a t e 48 56 64 72 80 84 4 12 20 28 36 44 52 60 68 76 92 88 Number o f p a tients a t risk 18 12 10 7 5 4 4 4 4 4 2 17 12 8 5 4 4 4 4 4 3 1 1 Median OS (95% CI, 13.1-NE) 35 . 7 months
  • Median OS follow-up was 27.1 months3
  • 87% survival rate at 12 months per Kaplan-Meier estimation3
  • Because there was no control arm in this study, OS results should be interpreted cautiously1

AML, acute myeloid leukemia; OS, overall survival.

11% of patients treated with TIBSOVO progressed from MDS to AML.3
See the safety profile of TIBSOVO

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2022 2. Servier announces FDA approval of TIBSOVO® (ivosidenib tablets) for the treatment of IDH1-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS). Servier Pharmaceuticals LLC. Published October 24, 2023. Accessed March 16, 2024. https://servier.us/blog/servier-announces-fda-approval-of-tibsovo-ivosidenib-tablets-for-the-treatment-of-idh1-mutated-relapsed-or-refractory-r-r-myelodysplastic-syndromes-mds/ 3. Data on file. Servier Pharmaceuticals LLC.

TIBSOVO was evaluated in an open-label, single-arm, multicenter study1

Key inclusion criteria2
  • Age ≥18 years
  • Must have had R/R MDS with IDH1 R132 gene mutation
  • ECOG PS grade of 0-2
  • Platelet count ≥20,000/μL (transfusions allowed)
  • Adequate hepatic and renal function
Key exclusion criteria2
  • Previous treatment with an IDH1 inhibitor and progressed on therapy
  • Had HCT within 60 days of first dose of ivosidenib, are on immunosuppressive therapy post HCT, or have clinically significant GVHD
  • Received systematic anticancer therapy, radiotherapy, or investigational agent <14 days prior to starting treatment. Hydroxyurea was allowed
  • Patients with various cardiovascular considerations including, but not limited to, Class III or IV congestive heart failure, history of myocardial infarctions, unstable angina pectoris, history of ventricular arrhythmias, and QTc ≥450 msec or other QT prolongation risk
  • Patients with other forms of leukemias, including AML
Treatment did not require randomizations, blinding, or stratification.2
study-mds-timeline R/R MDS arm (parent trial) n=122 R/R MDS substudy n=72 TIBSOVO 500 mg QDcontinuous dosing x28-day cycles2 Relapse,progression,HCT, or otherprotocol criteria2 Survivalfollow-up2
  • The study design included a parent study and 2 substudies, including an MDS substudy that assessed the safety and tolerability, clinical activity, pharmacokinetics, and pharmacodynamics of TIBSOVO in patients with R/R MDS and an IDH1 mutation2
  • Efficacy was evaluated in 18 patients and safety was evaluated in 19 patients1

Efficacy was established on the basis of rate of complete remission (CR)a + partial remission (PR)b, duration of CR + PR, and rate of conversion from transfusion dependence to transfusion independence.1 All observed responses were CRs.

aCR was defined as bone marrow ≤5% myeloblasts with normal maturation of all cell lines, hemoglobin ≥11 g/dL, platelets ≥100 x 109/L, neutrophils ≥1.0 x 109/L, and response lasting at least 4 weeks.2 43% of CR responders had baseline bone marrow blasts <5%.1

bRate of CR or PR per 2006 Working Group response criteria for MDS.1

AML, acute myeloid leukemia; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GVHD, graft-versus-host disease; HCT, hematopoietic cell transplantation; IDH1, isocitrate dehydrogenase-1; QTc, corrected QT interval; R/R, relapsed or refractory.

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2023. 2. Data on file. Servier Pharmaceuticals LLC.

Baseline patient demographics and disease characteristics1

 
TIBSOVO® (500 mg daily)
(N=18)
Demographics
Median age, years (min, max) 74 (61, 82)
Age categories (%)
<65 years 17
≥65 years to <75 years 39
≥75 years 44
Sex, %
Male 78
Female 22
Race, %
White 78
Black or African American 6
Not reported 17
ECOG PS, %
0 28
1 56
2 17
IDH1 mutation,a %
R132C 50
R132H 28
R132G 11
R132L 6
R132S 6
Cytogenic risk status, %
Good 22
Intermediate 44
Poor 28
Missing 6
Baseline bone marrow blasts, %
<5% 39
≥5% 61
Prior therapies, %
Intensive chemotherapy 17
Nonintensive chemotherapy 83
1 line of HMA-based therapy 78
2 lines of HMA-based therapy 6

aUsing confirmatory Abbott RealTime IDH1 Assay testing results.

ECOG PS, Eastern Cooperative Oncology Group Performance Status; HMA, hypomethylating agent; IDH1, isocitrate dehydrogenase-1.

Reference: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2023.

 

Indication

TIBSOVO is indicated for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN MDS
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 MDS: 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 (eg, 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 relapsed or refractory MDS are creatinine increased, hemoglobin decreased, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash.

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 MDS patients.

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INDICATION

TIBSOVO is indicated for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Indication & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN MDS

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.