Summary of Product Characteristics: Information for the User

Brineura 150 mg Infusion Solution

Cerliponase Alfa

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this leaflet carefully before you receive this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you or your child experience any adverse effects, consult your doctor, even if they are not listed in this leaflet. See section 4.

Brineura contains the active ingredient cerliponase alfa, which belongs to a group of medications called enzyme replacement therapies. It is used to treat patients with neuronal ceroid lipofuscinosis type 2 (NCL2), also known as tripeptidyl-peptidase 1 (TPP1) deficiency.

People with NCL2 disease do not have an enzyme called TPP1, or have too little of it, and this results in an accumulation of substances called lysosomal storage materials. In people with NCL2 disease, these materials accumulate in certain parts of the body, especially in the brain.

How Brineura works

This medication replaces the missing enzyme, TPP1, thereby reducing the accumulation of lysosomal storage materials. This medication acts to slow the progression of the disease.

Do not administer Brineura:

• If you or your child have had an allergic reaction to cerliponase alfa or to any of the other components of this medication (listed in section 6) that could be potentially fatal, and the reactions returned when cerliponase alfa was administered again.
• If you or your child have a device implanted to drain excess fluid from the brain.
• If you or your child have signs of infection of the device or problems with it. Your doctor may decide to continue treatment once the infection or device problems have been resolved.

Warnings and precautions

Consult your doctor before Brineura is started for you or your child.

• You or your child may have problems with the implanted device used during treatment with Brineura (see section 4 "Possible side effects"), including infection or device failure. Treatment may be interrupted if the device needs to be changed or until the infection is cured. Consult your doctor if you have any questions about the device.
• Brineura may cause potentially fatal allergic reactions. Your doctor will monitor you or your child for symptoms of potentially fatal allergic reactions, such as hives, itching or redness, swelling of the lips, tongue, and/or throat, difficulty breathing, hoarseness, blue discoloration of the lips or fingers, low muscle tone, fainting, or incontinence.
• Your doctor will take your or your child's heart rate, blood pressure, respiratory rate, and temperature before, during, and after treatment. Your doctor may decide to perform additional monitoring if necessary.
• Your doctor will perform an electrocardiogram (ECG) every 6 months to rule out heart rhythm abnormalities. If you or your child have a history of heart problems, your doctor or nurse will monitor heart activity during each infusion.
• Your doctor may order cerebrospinal fluid samples to be analyzed for signs of infection.
• Brineura has not been administered to patients with advanced disease at the start of treatment or to children under 2 years old. Your doctor will discuss whether treatment with Brineura is suitable for you or your child.

Other medications and Brineura

Inform your doctor if you or your child are taking, have taken recently, or may need to take any other medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before treatment with this medication.

Do not receive treatment with Brineura during pregnancy unless it is clearly necessary. It is unknown whether Brineura passes into breast milk. Breastfeeding should be discontinued during treatment with Brineura. It is unknown whether Brineura affects human fertility.

Driving and operating machines

It is unknown whether Brineura will affect the ability to drive or operate machines. Consult your doctor.

Brineura contains sodium:

This medication contains 44 mg of sodium per vial, which should be taken into account in patients with low-sodium diets.

You or your child will have to undergo surgery to implant the device used to administer Brineura. The device helps the medication reach a specific part of the brain.

A doctor with knowledge of medication administration through intracerebroventricular perfusion (perfusion in the fluid in the brain) will administer Brineura to you in a hospital or clinic.

Brineura has not been administered to patients under 2 years old or over 8 years old (at the start of the clinical trial). Experience in children under 2 years is limited to a few children.

The recommended dose of Brineura that will be administered to you in alternate weeks depends on your age or that of your child:

• from birth to <6 years
• from 6 months to <1 year
• from 1 year to <2 years
• ≥ 2 years: 300 mg

Your doctor may adjust your dose or that of your child, or the time it takes to administer the medication, if the perfusion is not tolerated, an allergic reaction occurs, or there is a possible increase in brain pressure.

The medication is slowly pumped through the implanted device. After administering the medication, a shorter perfusion of a solution is performed to draw the remaining Brineura from the perfusion equipment to the brain. The administration of the medication and the solution will take between 2 hours and 4 hours and 30 minutes, approximately, depending on your or your child's dose. Your doctor may lower the dose or the perfusion speed based on your response during treatment.

Your doctor may give you or your child medications, such as antipyretics to lower fever or antihistamines to treat allergic reactions, before each treatment with Brineura to reduce the adverse effects that may occur during treatment or shortly after.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Consult your doctor or nurse immediately if you experience any of the following side effects:

Very common side effects (may affect more than 1 in 10 people):

• Fever
• Vomiting
• Irritability
• Seizures
• Reactions during or shortly after administration, such as, for example, hives, itching, or redness, swelling of the lips, tongue, and/or throat, difficulty breathing, hoarseness, blue discoloration of the lips or fingers, low muscle tone, fainting, or incontinence.

Common side effects (may affect up to 1 in 10 people):

• Bacterial infections related to the device
• Slower heart rate
• Incorrect device function due to a detected obstruction during preparation for infusion

Unknown frequency (cannot be estimated from available data)

• The device moves and does not function correctly when preparing for infusion

This medicine may cause other side effects:

Very common side effects:

• Headache
• Increased or decreased proteins in the cerebrospinal fluid
• Abnormal ECG results
• Increased cells in the cerebrospinal fluid detected in laboratory tests
• Upper respiratory tract infection (common cold)
• Problems with the catheter (the infusion catheter comes out of the implanted device)

Common side effects:

• Pain
• Rash on the skin
• Hives
• Head drop (where the chin falls onto the chest)
• Abdominal pain
• Leakage in the device
• Blisters in the mouth or tongue
• Swelling or redness of the eyelid and the white part of the eye
• Nervousness
• Gastrointestinal disorder

Reporting of side effects

If you or your child experience side effects, consult your doctor, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date, which appears on the vials and on the box after CAD. The expiration date is the last day of the month indicated.

Store in the freezer in a vertical position (between -25 °C and -15 °C). Transport and distribute frozen (between -85 °C and -15 °C). Store in the original container to protect it from light.

Once thawed, Brineura and the washing solution must be used immediately. The medication should only be extracted from the vials without opening immediately before use. If it cannot be used immediately, the unopened vials of Brineura or the washing solution should be stored at 2-8 °C and used before 24 hours.

Chemical and physical stability of the medication has been demonstrated during use for a period of up to 12 hours at room temperature (19-25 °C). For microbiological reasons, opened vials or the medication contained in syringes should be used immediately. If not used immediately, storage times during use and pre-use conditions are the responsibility of the user

The doctor or pharmacist is responsible for storing Brineura. They are also responsible for disposing of any unused amount of Brineura correctly.

Composition of Brineura

• The active ingredient is cerliponase alfa. Each vial of Brineura contains 150 mg of cerliponase alfa in 5 ml of solution. Each ml of perfusion solution contains 30 mg of cerliponase alfa.

• The other components of Brineura and the washing solution are: sodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate monohydrate, sodium chloride, potassium chloride, magnesium chloride hexahydrate, calcium chloride dihydrate, and water for injection preparations (see section 2 "Brineura contains sodium").

Appearance of Brineura and contents of the packaging

Brineura and the washing solution are perfusion solutions. The solutions are colorless or pale yellow, transparent or slightly opalescent; on occasion, the Brineura solution may contain translucent fibers or opaque particles.

Package size: 3 vials (two vials of Brineura and one vial of the washing solution), each containing 5 ml of solution.

Marketing authorization holder and manufacturer

BioMarin International Limited

Shanbally, Ringaskiddy

County Cork

Ireland

Last review date of this leaflet: MM/AAAA

This medicine has been authorized under "exceptional circumstances". This type of authorization means that due to the rarity of the disease, it has not been possible to obtain complete information about this medicine.

The European Medicines Agency will review any new information available for this medicine annually and this leaflet will be updated as necessary.

Other sources of information

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu There are also links to other websites about rare diseases and orphan medicines.