Safety Profile of ICLUSIG (ponatinib) in the OPTIC Trial

Determination of safety using a response-based dosing strategy in patients with CP-CML1

Adverse reactions  (≥10% among patients with CP-CML who received ICLUSIG 45 mg → 15 mg (n=94)1

Adverse reactions seen in the CML OPTIC Trial. ARs include rash, dry skin, hypertension, arterial occlusive events, hemorrhage, arthralgia, hyperlipidemia, abdominal pain, pancreatitis, constipation, hepatoxicity, headache, pyrexia, fatigue or asthenia, cardiac arrhythmias, and cardiac failure.

aArthralgia includes arthralgia, arthritis, back pain, intervertebral disc degeneration, osteoarthritis, pain, neck pain, pain in extremity, pain of skin, sciatica, spinal pain, tendonitis, and tenosynovitis.1

bHyperlipidemia includes blood cholesterol increased, blood triglycerides increased, dyslipidemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, and low density lipoprotein increased.1

cAbdominal pain includes abdominal discomfort, abdominal distension, abdominal pain, abdominal pain lower, abdominal pain upper, chronic gastritis, colitis, enteritis, enterocolitis, gastric ulcer, gastritis, gastroenteritis, gastrointestinal pain, gastroesophageal reflux disease, and Helicobacter gastritis.1

Serious Adverse Reactions1

Serious adverse reactions occurred in 34% of patients who received ICLUSIG at a starting dose of 45 mg. Serious adverse reactions in >2% of patients included AOEs (9%; of which 2.1% were sudden death), cardiac arrhythmias (6%), thrombocytopenia (5%), pyrexia (4.3%), anemia (3.2%), abdominal pain (3.2%), atrial fibrillation (2.1%), pancreatitis/lipase elevation (2.1%), neutropenia (2.1%), and hypertension (2.1%). Fatal adverse reactions occurred in 2 patients (2.1%), both of which were sudden death.

Arterial Occlusive Events1

  • 14% of patients experienced AOEs, of which 7%, 4.3%, and 2.1% experienced cardiovascular, cerebrovascular or peripheral vascular AOEs, respectively
    • Grade 3 or 4 AOEs occurred in 6% of patients; the most frequent Grade 3 or 4 AOEs were myocardial infarction, acute coronary syndrome, arterial thrombosis, ischemic stroke, ischemic cerebral infarction, and unstable angina (1.1% each) 

Discontinuation Rates1

Permanent discontinuation of ICLUSIG due to an adverse reaction occurred in 19% of patients who received ICLUSIG at a starting dose of 45 mg. Adverse reactions which resulted in discontinuation in >2% of patients included AOEs, thrombocytopenia, hypertension, and sudden death.

ICLUSIG demonstrated efficacy in CML in OPTIC

ICLUSIG uses response-based dosing to balance benefit-risk profile

AOE=arterial occlusive event; CML=chronic myeloid leukemia; CP‑CML=chronic-phase chronic myeloid leukemia; CTCAE=common terminology criteria for adverse events.