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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 or longer and 37% were exposed for greater than 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 AbnormalitiesAll Grades %Grade ≥3 %
Hematology abnormalities
Decreased platelets6421
Decreased hemoglobin5523
Decreased neutrophils5425
Decreased lymphocytes3411
Increased activated partial thromboplastin time141
Increased lymphocytes100
Chemistry abnormalities
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.


Safety Profile in PATHFINDER 3-year follow-up2‡


Adverse reactions occurring in patients with advanced SM during the PATHFINDER 3-year follow-up (N=107)

TRAEs in ≥15% of safety population (n=107)

Adverse Events, n (%)Treatment-related AEs
All Grades
Hematologic AEs
Thrombocytopeniaf43 (40)
Anemiaf34 (32)
Neutropeniaf20 (19)
Non hematologic AEs
Periorbital edema44 (41)
Peripheral edema41 (38)
Cognitive disorder18 (17)
Eyelid edemaf18 (17)
Hair color changes18 (17)
Face edema17 (16)
  • Dose reductions, interruptions, and discontinuations due to TRAEs occurred in 76%, 63%, and 13% of patients, respectively
  • Treatment-related cognitive disorder occurred in 17% of patients, remained consistent with prior data,§ and were mostly Grade 1–2
  • Over the 3-year follow-up, 4 patients (3.7%) experienced intracranial bleeds
  • As of September 15, 2023, no treatment-related deaths were reported

‡Data cutoff: September 15, 2023.

§Data cutoff: September 9, 2022.

fPooled terms.

  AE, adverse events; TRAE, treatment-related adverse events.

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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

References: 1. AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; November 2024. 2. Data on file. Blueprint Medicines Corporation, Cambridge, MA.

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INDICATION

AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with advanced SM (AdvSM) including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

Limitations of Use: AYVAKIT is not recommended for the treatment of patients with AdvSM with platelet counts of <50 x 109/L.

IMPORTANT SAFETY INFORMATION
INDICATION & IMPORTANT SAFETY INFORMATION

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 AdvSM 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.

A platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in AdvSM patients with platelet counts <50 x 109/L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction.

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 and indication, 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 a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks following the final dose.

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

Drug Interactions—Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inducers. If contraception requires estrogen, limit ethinyl estradiol to ≤20 mcg unless a higher dose is necessary.

To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

AYVAKIT is available in 25-mg, 50-mg, 100-mg, and 200-mg tablets.

Please click here to see the full Prescribing Information for AYVAKIT.