ADVSM SAFETY

AYVAKIT was generally well tolerated in clinical trials1

MAJORITY OF ADVERSE REACTIONS WERE GRADE 1 OR 21

The safety of AYVAKIT was evaluated in 148 patients in EXPLORER and PATHFINDER. Patients received a starting dose of AYVAKIT ranging from 30 mg to 400 mg orally once daily and were centrally confirmed to have Advanced SM (N=131), including 80 patients who received the recommended starting dose of 200 mg once daily.

Among patients receiving AYVAKIT, 70% were treated for ≥6 months and 37% were exposed for >1 year.

Fatal adverse reactions occurred in 2.5% [2/80] of patients receiving the recommended starting dose of 200 mg.1 No specific adverse reaction leading to death was reported in more than 1 patient.1

10% of patients permanently discontinued due to any adverse reaction at the recommended starting dose of 200 mg.1

Serious adverse reactions were seen in 34% of patients receiving the recommended starting dose of 200 mg (N=80).1

The most common adverse reactions (≥20%) were edema, diarrhea, nausea, and fatigue/asthenia.1

ADVERSE REACTIONS AND LAB ABNORMALITIES (≥10%) FOR PATIENTS RECEIVING 200 MG ONCE-DAILY STARTING DOSE IN EXPLORER AND PATHFINDER (N=80)1*a
Adverse ReactionAll Grades %Grade ≥3 %
General
Edemab795
Fatigue/asthenia234
Gastrointestinal
Diarrhea281
Nausea241
Vomiting183
Abdominal painc141
Constipation110
Nervous system
Headache150
Cognitive effectsd141
Taste effectse130
Dizziness130
Musculoskeletal and connective tissue
Arthralgia101
Respiratory, thoracic and mediastinal
Epistaxis110
Laboratory AbnormalityAll Grades %Grade ≥3 %
Hematology
Decreased platelets6421
Decreased hemoglobin5523
Decreased neutrophils5425
Decreased lymphocytes3411
Increased activated partial thromboplastin time141
Increased lymphocytes100
Chemistry
Decreased calcium503
Increased bilirubin413
Increased aspartate aminotransferase381
Decreased potassium264
Increased alkaline phosphatase245
Increased creatinine200
Increased alanine aminotransferase181
Decreased sodium181
Decreased albumin151
Decreased magnesium141
Increased potassium110

Clinically relevant adverse reactions occurring in <10% of patients were: cardiac failure (2.5%), cardiac failure congestive (1.3%), ascites (5%), gastrointestinal hemorrhage (1.3%), large intestine perforation (1.3%), cholelithiasis (1.3%), upper respiratory tract infection (6%), urinary tract infection (6%), herpes zoster (2.5%), flushing (3.8%), hypertension (3.8%), hypotension (3.8%), hot flush (2.5%), insomnia (6%), pain in extremity (6%), dyspnea (9%), cough (2.5%), rash† (8%), alopecia (9%), pruritus (8%), hair color changes (6%), decreased appetite (8%), lacrimation increased (9%), and decreased phosphate (9%).

*Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) versions 4.03 and 5.0.

†Grouped term including rash and rash maculopapular.

aSelect laboratory abnormalities (≥10%) worsening from baseline in patients with Advanced SM.

bEdema includes face swelling, eyelid edema, orbital edema, periorbital edema, face edema, peripheral edema, edema, generalized edema, and peripheral swelling.

cAbdominal pain includes abdominal pain, upper abdominal pain, and abdominal discomfort.

dCognitive effects include memory impairment, cognitive disorder, confusional state, delirium, and disorientation.

eTaste effects include dysgeusia.

WARNINGS AND PRECAUTIONS1

Intracranial hemorrhage
Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (e.g., subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT in clinical trials. In Advanced SM patients who received AYVAKIT at 200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts.

Monitor patients closely for risk factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia. Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH.

Permanently discontinue AYVAKIT if ICH of any grade occurs.

Cognitive effects
Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 33% of 995 patients overall in patients who received AYVAKIT in clinical trials including 28% of 148 AdvSM patients (3% were Grade ≥3).

Depending on the severity, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.

Photosensitivity
AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients.

Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment.

Embryo-fetal toxicity
AYVAKIT can cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 weeks after the final dose.

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See the recommended dosing instructions for AYVAKIT, including guidance for patient monitoring and dose and therapy management for adverse reactions.
LEARN HOW TO DOSE AYVAKIT