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Patient demographics

TIBSOVO® 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%
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
ECOG PS, Eastern Cooperative Oncology Group Performance Status.

Many patients in the study had challenging disease characteristics1,2

  • 26%

    of patients who were refractory in relapse1

  • 37%

    of patients who were primary refractory1

58% of patients had ≥2 prior anticancer therapies2

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

23% of patients had prior stem cell transplantation for AML1
33% of patients had secondary AML1

Study design
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Rates of CR and CRh

TIBSOVO delivered strong and durable responses as an oral, single agent in difficult-to-treat disease1

  • 24.7% CR rate (43/174) (95% CI, 18.5-31.8);
    8.0% CRh rate (14/174) (95% CI, 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
  • For patients who achieved CR or CRh, the median time to CR or CRh was 2 months (range, 0.9-5.6 months)1
47% of patients who had received 1 prior regimen (35/74) achieved CR or CRh (95% CI, 35.6-59.3)2
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Duration of response
Medium Duration of Response, Graph
  • Median treatment duration: 4.1 months (range, 0.1-39.5 months)1
  • Median follow-up: 8.3 months (range, 0.2-39.5 months)1
bDOCR (duration of CR) and DOCR+CRh (duration of CR+CRh) were defined as time since first response of CR or CR/CRh, respectively, to relapse or death, whichever is earlier.1
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Transfusion independence

Transfusion independence was seen in 37% of transfusion-dependent patients who received TIBSOVO1

  • 20.0% (22/110)

    Patients who achieved CR or CRh2

  • 17.3% (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 RBC 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 period1
12% of patients (21/174) went on to receive a stem cell transplant following treatment with TIBSOVO1
RBC, red blood cell.

References: 1. TIBSOVO [package insert]. Cambridge, MA: Agios Pharmaceuticals, Inc.; 2019. 2. Data on file. Agios Pharmaceuticals, Inc.
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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 on 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]. Cambridge, MA: Agios Pharmaceuticals, Inc.; 2019.
 

Indications

TIBSOVO is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

  • Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
  • Adult patients with relapsed or refractory AML.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME
Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. 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: See Boxed WARNING. In the clinical trial, 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. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. 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 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. One patient developed ventricular fibrillation attributed to TIBSOVO. 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, 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 occurred in <1% (2/258) of patients treated with TIBSOVO in the clinical study. 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 (≥20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).
  • In patients with newly diagnosed AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (≥5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
  • In patients with relapsed or refractory AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).

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 at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

 

INDICATIONS

TIBSOVO is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

  • Adult patients with newly diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Indications & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. 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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