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Patient demographics

TIBSOVO (ivosidenib tablets) monotherapy was studied in a patient population reflective of that seen in clinical practice1

Selected baseline demographic and disease characteristics (N=174)1
Median age, years (min, max) 67 (18, 87)
ECOG PS
0 21%
1 56%
2 22%
3 1%
IDH1 mutation
R132C 59%
R132H 25%
R132G 7%
R132S 6%
R132L 4%
Cytogenetic risk status
Intermediate 60%
Poor 27%
Missing/unknown 13%
Relapse type
Primary refractory 37%
Refractory relapse 26%
Untreated relapse 37%
Prior stem cell transplantation for AML 23%
Transfusion dependent at baselinea 63%
Type of AML
De novo AML 67%
Secondary AML 33%

AML, acute myeloid leukemia; ECOG PS, Eastern Cooperative Oncology Group Performance Status; IDH1, isocitrate dehydrogenase-1; RBC, red blood cell.

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

Many patients in the study had challenging disease characteristics1,2

26%

63% of patients (109/174) were refractory to therapy1

26%
Patients who were refractory in relapse1

37%
Patients who were primary refractory1

58% of patients had ≥2 prior anticancer therapies2

  • Median number of prior therapies (min, max): 2 (1, 6)1

33% of patients had secondary AML1

23% of patients had prior stem cell transplantation for AML1

87% of patients had intermediate or poor cytogenic risk status1

Study design
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RATES OF CR AND CRh

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

25%

33% of patients (57/174) achieved CR or CRh (95% CI, 25.8‑40.3)1

25% (43/174) achieved CR (95% Cl, 18.5‑31.8)1

8% (14/174) achieved CRh (95% Cl, 4.5‑13.1)1

  • CR+CRh rate appeared to be consistent across all baseline demographic and baseline disease characteristics with the exception of number of prior regimens1

AML, acute myeloid leukemia.

Patients achieved CR or CRh after receiving 1 or more prior regimens2

47%

47% of R/R patients who had received 1 prior regimen (35/74) achieved CR or CRh (95% CI, 35.6-59.3)2

30%

30% of R/R patients who had received 2 prior regimens (15/50) achieved CR or CRh (95% CI, 17.9-44.6)2

15%

15% of R/R patients who had received ≥3 prior regimens (7/48) achieved CR or CRh (95% CI, 6.1-27.8)2

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/µL and absolute neutrophil counts >1000/µL)2; 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/µL and absolute neutrophil counts >500/µL)2; R/R. relapsed or refractory.

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Duration of response

TIBSOVO monotherapy provided durable responses1

Medium Duration of Response, Graph Medium Duration of Response, Graph

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

36% of patients who achieved CR or CRh had ongoing responses with TIBSOVO at 12 months based on Kaplan-Meier estimation2

  • Median treatment duration: 4.1 months (range, 0.1-39.5)1
  • Median follow-up: 8.3 months (range, 0.2-39.5)1
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Time to Response

TIBSOVO monotherapy enabled strong and rapid responses1,3

Time to response in patients who achieved CR or CRh

timeline timeline

TIME (MONTHS)

Median time to first response: 1.9 months (range, 0.8‑4.7)3

Median time to CR or CRh: 2 months (range, 0.9‑5.6)1

Latest CR or CRh was achieved: 5.6 months1

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

Earliest CR or CRh was achieved: 0.9 months1

  • 100% of patients taking TIBSOVO who achieved CR or CRh reached this milestone within 6 months1
  • For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response1
Transfusion independence

Transfusion independence was seen in 37% of transfusion-dependent patients who received TIBSOVO monotherapy1

37%

37% of patients who were transfusion dependent at baseline (41/110) became transfusion independent1

20% (22/110) Patients who achieved CR or CRh2

17% (19/110) Patients who did not achieve CR or CRh2

59% of patients who were transfusion independent at baseline (38/64) remained so1

Patients were defined as transfusion dependent at baseline if they received any red blood cell or platelet transfusions 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-consecutive day postbaseline period.1

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Hematologic Improvement

TIBSOVO monotherapy enabled improvements in key hematologic parameters3

TIBSOVO demonstrated an improvement in hematologic variables together with a reduction in bone marrow blasts

INCREASE IN MEAN PLATELET COUNT AND MEAN ABSOLUTE NEUTROPHIL COUNTS

graph graph

INCREASE IN MEAN HEMOGLOBIN LEVEL, DECREASE IN MEAN BONE MARROW BLASTS

graph graph

Adapted with permission from DiNardo et al.3
Data are mean values with standard deviations.

12% of patients (21/174) went on to receive a stem cell transplant following treatment with TIBSOVO1

Learn about the TIBSOVO safety profile

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2022. 2. Data on file. Servier Pharmaceuticals LLC. 3. DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386-2398. doi:10.1056/NEJMoa1716984

 
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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 differentiation1,2

  • The pivotal trial for TIBSOVO monotherapy 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 TIBSOVO1,3
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

AML, acute myeloid leukemia; 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/µL and absolute neutrophil counts ≥1000/µL)2; 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/µL and absolute neutrophil counts >500/µL)2; IC, intensive chemotherapy; IDH1, isocitrate dehydrogenase-1; R/R, relapsed or refractory.1

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2022. 2. Data on file. Servier Pharmaceuticals LLC. 3. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). U.S. Food and Drug Administration. Updated June 30,2022. Accessed August 12, 2022. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
 

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.