General Information

Tibsovo (ivosidenib) is an isocitrate dehydrogenase-1 (IDH1) inhibitor.

Tibsovo is specifically indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:

Acute Myeloid Leukemia (AML)

Newly-diagnosed AML who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy
Relapsed or refractory AML

locally advanced or metastatic cholangiocarcinoma who have been previously treated

Tibsovo is supplied as a tablet for oral administration. The recommended dose is 500 mg taken orally once daily until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response. Administer Tibsovo with or without food. Do not administer Tibsovo with a high-fat meal because of an increase in ivosidenib concentration. Do not split or crush tablets. Administer tablets orally about the same time each day. If a dose of Tibsovo is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours.

Side Effects

Adverse effects associated with the use of Tibsovo in patients with cholangiocarcinoma may include, but are not limited to, the following:

fatigue

nausea

abdominal pain

diarrhea

cough

decreased appetite

ascites

vomiting

anemia

rash

Adverse effects associated with the use of Tibsovo in patients with AML may include, but are not limited to, the following:

fatigue

leukocytosis

arthralgia

diarrhea

dyspnea

edema

nausea

mucositis

electrocardiogram QT prolonged

rash

pyrexia

cough

constipation

The Tibsovo drug label comes with the following Black Box Warning: 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.

Indication 1 - for the treatment of patients with acute myeloid leukemia with a susceptible IDH1 mutation

approved July 2018

Clinical Trial Results

The FDA approval of Tibsovo was based on a single-arm trial of 174 adult patients with relapsed or refractory AML with an IDH1 mutation. Tibsovo was given orally at a starting dose of 500 mg daily until disease progression, development of unacceptable toxicity, or undergoing hematopoietic stem cell transplantation. The trial measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment (complete remission or CR), as well as patients with no evidence of disease and partial recovery of blood counts after treatment (complete remission with partial hematologic recovery or CRh). With a median follow-up of 8.3 months, 32.8% of patients experienced a CR or CRh that lasted a median 8.2 months. Of the 110 patients who required transfusions of blood or platelets due to AML at the start of the study, 37% went at least 56 days without requiring a transfusion after treatment with Tibsovo.

Indication 2 - for the treatment of patients with IDH1-mutant cholangiocarcinoma

approved August 2021

Clinical Trial Results

The FDA approval was based on the ClarIDHy study, a randomized Phase 3 trial for previously treated IDH1-mutated cholangiocarcinoma. Results from the ClarIDHy study demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS) by an independent review committee. The median PFS for Tibsovo and placebo was 2.7 and 1.4 months, respectively. Thirty-two percent and 22% of patients randomized to Tibsovo remained free of progression or death at 6 and 12 months, respectively, versus none on the placebo arm. The study protocol specified that patients randomized to placebo could cross over to Tibsovo at the time of disease progression, and a high proportion of patients in the placebo arm (70.5%) crossed over to Tibsovo . The study also showed the key secondary endpoint of overall survival (OS) favoring patients randomized to Tibsovo compared to those randomized to placebo; however, statistical significance was not reached. OS results are based on the final analysis of OS (based on 150 events which occurred 16 months after the final analysis of PFS. The median OS for Tibsovo was 10.3 months; and placebo was 7.5 months without adjusting for crossover.