Safety Profile of ICLUSIG (ponatinib) in the OPTIC trial
5-Year Follow-up Analysis: Safety Profile of ICLUSIG (ponatinib) in the OPTIC trial
Adverse reactions (≥10%) among patients with CP-CML who received ICLUSIG 45 mg → 15 mg (n=94)1
aArthralgia includes arthralgia, back pain, osteoarthritis, pain, neck pain, pain in extremity, spinal pain, tendonitis, bone pain, musculoskeletal pain, chondrocalcinosis, enthesopathy, pain in jaw.1
bHyperlipidemia includes blood cholesterol increased, blood triglycerides increased, dyslipidemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, low density lipoprotein increased.1
cAbdominal pain includes abdominal distension, abdominal pain, abdominal pain upper, chronic gastritis, duodenal ulcer, duodenitis, duodenogastric reflux, dyspepsia, gastric ulcer, gastritis, gastroenteritis, gastrointestinal pain, helicobacter gastritis, peptic ulcer.1
CTCAE=Common Terminology Criteria for Adverse Events. AOE=arterial occlusive event.
Serious Adverse Reactions1
Serious adverse reactions occurred in 40% of patients who received ICLUSIG at a starting dose of 45 mg. Serious adverse reactions in >2% of patients included AOEs (13%; of which 2.1% were sudden death), cardiac arrhythmias (9%; of which 2.1% were atrial fibrillation), thrombocytopenia (5%), pyrexia (4.3%), anemia (3.2%), abdominal pain (3.2%), pancreatitis/lipase elevation (2.1%), neutropenia (2.1%), hypertension (2.1%) and hepatotoxicity (2.1%). Fatal adverse reactions occurred in 4 patients (4.3%), including sudden death (2.1%), myocardial infarction (1.1%), and myocardial ischemia (1.1%).
Arterial Occlusive Events1
- 18% of patients experienced AOEs, of which 11%, 4.3%, and 3.2% experienced cardiovascular, cerebrovascular or peripheral vascular AOEs, respectively
- Grade 3 or 4 AOEs occurred in 7% of patients; the most frequent Grade 3 or 4 AOEs were myocardial infarction, acute coronary syndrome, arterial thrombosis, ischemic stroke, ischemic cerebral infarction, subclavian artery stenosis, and unstable angina (1.1% each)
- Fatal AOEs occurred in 4 patients (4.3%); including sudden death (2.1%), myocardial ischemia (1.1%), and myocardial infarction (1.1%).
Discontinuation Rates1
Permanent discontinuation of ICLUSIG due to an adverse reaction occurred in 24% 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.
5-Year Follow-Up Analysis: Optimized Dosing, Proven Safety Profile
ICLUSIG uses optimized dosing to help with dose modification upon clinical benefit1, 2
By Year 5, safety results were consistent with those of the primary analysis of OPTIC
bAll treatment-emergent AEs with "drug withdrawn" as the action taken
Fatal AOEs occurred in 4.3% of patients, and 7.4% of patients experienced Grade 3/4 TE-AOEs
6.4% of patients experienced Grade 3/4 TE-AOEs after a median follow-up of 27.0 months [or "~2 years"] (primary analysis).
An additional patient (1.1%) experienced a Grade 3/4 TE-AOE as of the 5-year follow-up analysis.
ICLUSIG demonstrated efficacy in CP-CML in OPTIC
ICLUSIG uses optimized 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.