The safety of AYVAKYT was evaluated in patients with ISM in PIONEER
Patients received a starting dose ranging from 25 mg to 100 mg orally once daily, including 141 patients who received the recommended dose of 25 mg in Part 2, the pivotal part of PIONEER:1
The most common adverse reactions reported in the AYVAKYT + BSC treatment arm were peripheral oedema (12%) and flushing (9%), of which almost all were Grade 1 or 2*
94% of peripheral oedema reactions and 90% of face oedema reactions reported were Grade 1 – none were Grade ≥3 or led to treatment discontinuation
No serious adverse reactions or fatal adverse reactions occurred in 141 patients receiving AYVAKYT + BSC
Fewer than 1% of AYVAKYT-treated patients discontinued due to any adverse reactions1
Patients receiving AYVAKYT + BSC had fewer episodes of anaphylaxis over time (5% during the screening period vs 1% during Part 2)
*The severity of adverse reactions graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and 5.0.
25 mg AYVAKYT daily is well tolerated, with a clinical safety profile comparable to BSC + placebo1,2
Adverse reactions reported in clinical studies in patients with ISM treated with AYVAKYT1
Please refer to the SmPC for a full list of adverse reactions
Adverse reactions reported in clinical studies of AYVAKYT in patients with ISM1*
| Adverse reactions | AYVAKYT 25 mg + BSC All grades (%) |
Grades ≥3 (%) |
| Psychiatric disorders | ||
| Insomnia | 5.7 | – |
| Vascular disorders | ||
| Flushing | 9.2 | 1.4 |
| Skin and subcutaneous tissue disorders | ||
| Photosensitivity reaction | 2.8 | – |
| General disorders and administration site conditions | ||
| Peripheral oedema** | 12.1 | – |
| Face oedema | 7.1 | – |
| Investigations | ||
| Blood alkaline phosphatase increased | 6.4 | 0.7 |
*The severity of adverse reactions graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and 5.0.
**Peripheral oedema (including oedema peripheral and peripheral swelling).
Special warnings and precautions for use1
AYVAKYT at higher doses has been associated with an increased incidence of haemorrhagic adverse reactions, including serious and severe adverse reactions, like gastrointestinal haemorrhage and intracranial haemorrhage.
Serious intracranial haemorrhage may occur with AYVAKYT treatment. No events of intracranial haemorrhage occurred in 141 patients with ISM receiving 25 mg of AYVAKYT during the 24-week duration of Part 2 of the PIONEER study. For patients with observed intracranial haemorrhage during treatment with AYVAKYT in any indication, regardless of severity grade, AYVAKYT must be permanently discontinued.
Cognitive effects, such as memory impairment, cognitive disorder, confusional state and encephalopathy, can occur in patients receiving AYVAKYT. The mechanism of the cognitive effects is not known.
In patients with ISM, cognitive effects can be one of the disease symptoms. Patients with ISM must notify their healthcare professional if they experience new or worsening cognitive symptoms.
In patients with ISM, localised oedemas (peripheral, facial) have been reported with a frequency category of at least common.
In patients with ISM, interval assessments of QT by electrocardiogram (ECG) should be considered, in particular in patients with concurrent factors that could prolong QT (e.g. age, pre-existing heart rhythm disorders).
Co-administration with strong or moderate CYP3A inhibitors should be avoided because it may increase the plasma concentration of AYVAKYT. Co-administration with strong or moderate CYP3A inducers should be avoided because it may decrease the plasma concentrations of AYVAKYT.
Exposure to direct sunlight must be avoided or minimised, due to the phototoxicity risk associated with AYVAKYT. Patients must be instructed to use measures such as protective clothing and sunscreen with a high sun protection factor (SPF).
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet; that is to say it is essentially ‘sodium-free’.
Women of childbearing potential/contraception in males and females
Women of childbearing potential must be informed that AYVAKYT may cause foetal harm.
The pregnancy status of women of reproductive potential must be verified prior to initiating AYVAKYT treatment.
Women of childbearing potential must use effective contraception during treatment and for 6 weeks after the last dose of AYVAKYT. Males with female partners of childbearing potential must use effective contraception during treatment and for 2 weeks after the last dose of AYVAKYT.
Patients must be advised to contact their healthcare professional immediately if they become pregnant, or if pregnancy is suspected, while taking AYVAKYT.
Pregnancy
AYVAKYT is not recommended during pregnancy and in women of childbearing potential not using contraception.
If AYVAKYT is used during pregnancy or if the patient becomes pregnant while taking AYVAKYT, the patient must be advised of the potential risk to the foetus.
Breastfeeding
Breastfeeding must be discontinued during treatment with AYVAKYT and for 2 weeks following the final dose.
Reporting of adverse events
To report suspected adverse reactions, contact Blueprint Medicines (Netherlands) B.V. by calling +31 85 064 4001 or via email at MedInfoEurope@blueprintmedicines.com
Access the recommended dosing instructions for AYVAKYT in ISM
AYVAKYT Dosing for ISMBSC=best supportive care.
