Brineura

Generic name: cerliponase alfa
Drug class: Lysosomal enzymes

Medically reviewed by  A Ras MD.

What is Brineura?

Brineura is a prescription medicine that is used to slow the loss of being able to walk around in some children.

Description

Cerliponase alfa is a purified human enzyme produced by recombinant DNA technology in a Chinese hamster ovary cell line. The active substance is a recombinant human tripeptidyl peptidase-1 (rhTPP1), a lysosomal exopeptidase. The primary activity of the mature enzyme is the cleavage of N-terminal tripeptides from a broad range of protein substrates.

Cerliponase alfa contains 544 amino acids with an average molecular mass of 59 kDa. The mature enzyme is 368 amino acids in length. There are 5 consensus N-glycosylation sites on rhTPP1 that contain high mannose, phosphorylated high mannose and complex glycosylation structures.

Brineura (cerliponase alfa) Injection and Intraventricular Electrolytes Injection are administered by intraventricular infusion. The solutions are sterile, nonpyrogenic, and free of foreign particulates.  Brineura is a clear to slightly opalescent and colorless to pale yellow solution. Intraventricular Electrolytes is a clear to colorless solution.

Brineura and Intraventricular Electrolytes Injection are packaged in 10 mL clear Type 1 single-dose glass vials [see How Supplied/Storage and Handling (16)]. Each vial of Brineura provides 5 mL of solution containing 150 mg cerliponase alfa. Each vial of Intraventricular Electrolytes Injection provides 5 mL of solution. Both Brineura and Intraventricular Electrolytes Injection are formulated with the following excipients: calcium chloride dihydrate (1.05 mg); magnesium chloride hexahydrate (0.8 mg); potassium chloride (1.1 mg); sodium chloride (43.85 mg); sodium phosphate, dibasic, heptahydrate (0.55 mg); sodium phosphate, monobasic, monohydrate (0.4 mg); and Water for Injection, USP. The pH of the solution is between 6.2 to 6.8 for Brineura, and between 6.0 to 7.0 for Intraventricular Electrolytes Injection.

Each vial contains: sodium: 0.76 mEq, and potassium: 0.015 mEq.

Mechanism of Action

CLN2 disease is a neurodegenerative disease caused by deficiency of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1), which catabolizes polypeptides in the CNS. TPP1 has no known substrate specificity.  Deficiency in TPP1 activity results in the accumulation of lysosomal storage materials normally metabolized by this enzyme in the central nervous system (CNS), leading to progressive decline in motor function.

Cerliponase alfa (rhTTP1), a proenzyme, is taken up by target cells in the CNS and is translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor). Cerliponase alfa is activated in the lysosome and the activated proteolytic form of rhTPP1 cleaves tripeptides from the N-terminus of proteins.

Before taking Brineura, tell your doctor:

• If your child is allergic to Brineura; any part of this medicine; or any other drugs, foods, or substances. Tell the doctor about the allergy and what signs your child had.
• If your child has an infection in the brain or spine (central nervous system or CNS).
• If your child has had a shunt placed to lower pressure on the brain.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Brineura with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Brineura?

• Tell all of your child’s health care providers that your child is taking Brineura. This includes your child’s doctors, nurses, pharmacists, and dentists.
• Have your child’s blood pressure and heart rate checked often.
• Some people have unsafe allergic effects or bad side effects during the infusion or within 24 hours of the infusion. Talk with the doctor.
• Other drugs may be given before Brineura to help avoid side effects.
• Tell your child’s doctor right away if your child has problems with the device used to give Brineura. This includes leakage, device failure, or bulging of the scalp around or above the device. You will also need to tell your child’s doctor right away if your child has signs of an infection (like redness, tenderness, swelling, or discharge) on or around the device.

If your child is pregnant or breast-feeding a baby:

• Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.

How is Brineura best taken?

Give Brineura as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.

• It is given into the spinal fluid.

What do I do if I miss a dose?

• Call your child’s doctor to find out what to do.

What are the side effects of Brineura that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of meningitis like headache with fever, stiff neck, upset stomach, confusion, or if lights bother the eyes.
• A heartbeat that does not feel normal.
• Fast or slow heartbeat.
• Very bad dizziness or passing out.
• Seizures.
• Feeling irritable.
• Feeling jittery.
• Throwing up.

What are some other side effects of Brineura?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:

• Headache.

These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Brineura?

• If you need to store Brineura at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.

SRC: NLM .