BRINEURA

What it is

Brineura is a solution for injection containing cerliponase alfa at a concentration of 30 mg/mL. Each vial contains 150 mg of cerliponase alfa in 5 mL of solution. Cerliponase alfa is produced in mammalian Chinese Hamster Ovary cells. The pharmaceutical form is a solution for injection presented as a clear to slightly opalescent and colourless to pale yellow solution, which may occasionally contain thin translucent fibres or opaque particles.

Approved indications

— Treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease, also known as tripeptidyl peptidase 1 (TPP1) deficiency.

Dosing overview

The recommended dose is 300 mg cerliponase alfa administered once every other week by intracerebroventricular infusion. In patients less than 2 years of age, lower doses are recommended. For patients from birth to less than 6 months, the dose is 100 mg; from 6 months to less than 1 year, 150 mg; from 1 year to less than 2 years, 200 mg for the first 4 doses then 300 mg for subsequent doses; and 300 mg for patients 2 years and older. Brineura must only be administered by a trained healthcare professional knowledgeable in intracerebroventricular administration in a healthcare setting.

Key safety warnings

Intracerebroventricular access device-related infections, including sub-clinical and meningitis, have been observed in patients treated with Brineura. Meningitis may present with the following symptoms: fever, headache, neck stiffness, light sensitivity, nausea, vomiting, and change in mental status. Healthcare professionals should inspect the scalp for skin integrity to ensure the intracerebroventricular access device is not compromised prior to each infusion. Common signs of device leakage and device failure include swelling, erythema of the scalp, extravasation of fluid, or bulging of the scalp around or above the intraventricular access device. Anaphylactic reactions have been reported with Brineura use during clinical trials and during postmarketing use. Healthcare professionals should be aware of the possible symptoms of anaphylaxis such as: generalised hives, pruritus or flushing, swollen lips, tongue, and/or uvula, dyspnoea, bronchospasm, stridor, hypoxemia, hypotonia, syncope, diarrhoea or incontinence. As a precautionary measure, appropriate medical support should be readily available when Brineura is administered. If anaphylactic reactions occur, immediately discontinue the infusion and initiate appropriate medical treatment. Material degradation of the intracerebroventricular access device reservoir occurs after long periods of use as confirmed in benchtop testing and observed in clinical trials with approximately 4 years of use. Access device replacement should be considered prior to 4 years of regular administration of Brineura.

Contraindications

Life-threatening anaphylactic reaction to the active substance or to any of the excipients listed in section 6.1, if re-challenge is unsuccessful. CLN2 patients with ventriculo-peritoneal shunts. Brineura must not be administered as long as there are signs of acute intracerebroventricular access device leakage, device failure, or device-related infection.

Regulatory history

Brineura was first approved on 10 August 2018. The product is registered on the ARTG (ARTG 298672) as cerliponase alfa 150 mg/5 mL solution for injection vial with flushing solution vial, first listed 2018-08-28.