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Now approved in combination with azacitidine

For patients with newly diagnosed aml

TIBSOVO® is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

Prescribing Information Press Release more
Patient demographics

TIBSOVO® (ivosidenib tablets) was studied in patients with difficult-to-treat AML1

Selected baseline demographic and disease characteristics (N=28)1
Median age (years) (min, max) 77 (64, 87)
ECOG PS
0 21%
1 57%
2 18%
3 4%
ELN risk category
Intermediate 32%
Adverse 68%
Transfusion dependent at baselinea 61%
Type of AML
De novo AML 21%
AML-MRC 68%
Therapy-related AML 11%
Prior HMA for antecedent hematological disorder 46%

ECOG PS, Eastern Cooperative Oncology Group Performance Status; ELN, European LeukemiaNet; HMA, hypomethylating agent; MDS, myelodysplastic syndrome; MRC, myelodysplasia-related changes.

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

See efficacy data for secondary AML patients
  • Comorbidities that precluded the use of intensive induction chemotherapy included: baseline ECOG PS ≥2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin >1.5 times the upper limit of normal, or creatinine clearance <45 mL/min1

Many patients in the clinical trials had poor performance status and were not good candidates for myelosuppressive regimens1,2

79%

79% of patients (22/28) had secondary AML1

11%
Patients who had therapy-related AML1

68%
Patients who had AML-MRC1

46% of patients had prior HMA therapy for an antecedent hematologic disorder1

50% of patients had a history of MDS2

ECOG PS, Eastern Cooperative Oncology Group Performance Status; ELN, European LeukemiaNet; HMA, hypomethylating agent; MDS, myelodysplastic syndrome; MRC, myelodysplasia-related changes.
Study design
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Rates of CR and CRh

TIBSOVO delivered strong responses as a once-daily oral treatment in a difficult-to-treat disease1,2

29%

43% of patients (12/28) achieved CR or CRh (95% CI, 24.5‑62.8)1

29% (8/28) achieved CR (95% CI, 13.2‑48.7)1

14% (4/28) achieved CRh (95% CI, 4.0‑32.7)1

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Duration of response

TIBSOVO provided durable responses1

Median duration of response (months)1,b
DOCR DOCR+CRh
NE (95% CI, 4.2-NE) NE (95% CI, 4.2-NE)

b DOCR and DOCR+CRh were defined as time since first response of CR or CR/CRh, respectively, to relapse or death, whichever was earlier.1

Median DOCR and median DOCR+CRh were not estimable (NE), with 5 patients who achieved CR or CRh (42%) remaining on TIBSOVO treatment (treatment duration range, 20.3-40.9 months).1

  • 58% of those who achieved CR or CRh (7/12) were in remission at 12 months after initiating treatment2

CR, complete remission, defined as <5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets >100,000/microliter and absolute neutrophil counts >1000/microliter); CRh, complete remission with partial hematological recovery, defined as <5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil counts >500/microliter).1

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Duration of response

TIBSOVO enabled strong and rapid responses1,2

Time to response in patients who achieved CR or CRh

rapid response in months rapid response in months

TIME (MONTHS)

Median time to first response: 1.9 months (range, 0.9‑3.6)2

Median time to CR or CRh: 2.8 months (range, 1.9‑12.9)1

Earliest CR or CRh achieved: 1.9 months1

~1 month
Decrease in bone marrow blasts and increase in neutrophil counts3

Earliest time to first response: 0.9 months2

  • 92% of patients taking TIBSOVO who achieved CR or CRh (11/12) reached this milestone within 6 months1
  • The latest CR was achieved at 4.6 months2
  • For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response2
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Transfusion independence

Transfusion independence was seen in 41% of transfusion-dependent patients who received TIBSOVO1

41%

41% of patients who were transfusion dependent at baseline (7/17) became transfusion independent1

55% of patients who were transfusion independent at baseline (6/11) remained so1

Patients were defined as transfusion dependent at baseline if they received any RBC or platelet transfusion occurring within 56 days prior to the first dose of TIBSOVO. Patients were defined as transfusion independent if they became independent of transfusions during any 56-day postbaseline period.1

RBC, red blood cell.

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Hematologic Improvement

TIBSOVO enabled improvements in key hematologic parameters3

Mean bone marrow aspirate blasts decreased coincident with increased platelet, neutrophil, and hemoglobin valuesc

graph graph graph graph graph graph graph graph

Adapted with permission from Roboz GJ et al. Blood. 2020;135(7):463-471.3

c Data are mean values with standard deviations.

d One patient enrolled in the dose-escalation phase was positive for the IDH1-D54N mutation by local testing and was not positive for the IDH1-R132 mutation by the companion diagnostic test; this patient was therefore excluded from the efficacy analyses.

Efficacy in Secondary AML

TIBSOVO delivered strong and durable responses as a once-daily oral treatment in the secondary AML setting2

patients with sAML

41% of patients with sAML (9/22) achieved CR or CRh2

  • 56% of patients with sAML who achieved CR or CRh (5/9) were in remission at 12 months after initiating treatment2
patients with prior HMA therapy

31% of patients with prior HMA therapy (4/13) achieved CR or CRh2

  • 50% of patients with prior HMA therapy who achieved CR or CRh (2/4) were in remission at 12 months after initiating treatment2
See what TIBSOVO can do in the R/R setting

sAML, secondary AML.
References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2021. 2. Data on file. Servier Pharmaceuticals LLC. 3. Roboz GJ, DiNardo CD, Stein EM, et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood. 2020;135(7):463-471. doi: 10.1182/blood.2019002140

 
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TIBSOVO® was studied as a single agent in both the newly diagnosed and R/R AML settings1

TIBSOVO is a first-in-class agent that inhibits the mutant IDH1 enzyme to induce myeloid differentiation1

  • The pivotal trial for TIBSOVO was an open-label, single-arm, multicenter trial1
  • IDH1 mutations were identified by a local or central diagnostic test and confirmed retrospectively using the Abbott RealTimeTM IDH1 assay, which is the FDA-approved test for selection of patients with AML for treatment with TIBSOVO1
Patients were assigned a starting dose of TIBSOVO 500 mg daily and received treatment until disease progression, development of unacceptable toxicity, or undergoing hematopoietic stem cell transplantation1
  • 28 IC-ineligible patients with newly diagnosed AML were evaluated for safety and efficacy
  • 179 patients were evaluated for safety and 174 for efficacy in the R/R AML population

Efficacy was established based on the rate of CR and/or CRh, duration of CR+CRh, as well as the rate of conversion from transfusion dependence to transfusion independence1

CR, complete remission, defined as <5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets >100,000/microliter and absolute neutrophil counts >1000/microliter); CRh, complete remission with partial hematological recovery, defined as <5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil counts >500/microliter); IC, intensive chemotherapy; R/R, relapsed or refractory.1

Reference: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2021.
 

Indications

TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible 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

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: In the combination study AG120-C-009, 15% (11/71) of patients with newly diagnosed AML treated with TIBSOVO plus azacitidine experienced differentiation syndrome. 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. Of the 11 patients with newly diagnosed AML who experienced differentiation syndrome with TIBSOVO plus azacitidine, 8 (73%) recovered. Differentiation syndrome occurred as early as 3 days after start of therapy and during the first month on treatment.

In the monotherapy clinical trial AG120-C-001, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

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, or electrolyte abnormalities, or in 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

  • In patients with AML, the most common adverse reactions including laboratory abnormalities (≥25%) 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

Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for 1 month after the last dose.

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

 

INDICATIONS

TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible 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
  • Adult patients with relapsed or refractory AML.
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.

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