Cerliponase alfa

Cerliponase alfa contains an enzyme that occurs naturally in the body in healthy people. Some people lack this enzyme because of a genetic disorder. Cerliponase alfa replaces this missing enzyme in such people.

Cerliponase alfa is used to slow the loss of ability to crawl or walk in children with symptoms of a rare genetic condition called ceroid lipofuscinosis type 2 disease (CLN2), also called Batten disease. This medicine is for use in children who are at least 3 years old.

Batten disease is a rare genetic condition in which a person lacks the enzyme needed to break down certain materials in the body. These materials can build up in brain cells and cause problems with movement and coordination, delayed speech development, vision problems, seizures, and dementia.

Cerliponase alfa may help slow the loss of certain physical abilities in children with Batten disease. However, cerliponase alfa is not a cure for this condition.

Cerliponase alfa may also be used for purposes not listed in this medication guide.

Your child should not be treated with cerliponase alfa if he or she is allergic to it, or if the child has:

• complications with the surgically implanted catheter used to deliver this medicine; or

• a shunt in the brain (to help drain fluid build-up around the brain).

To make sure cerliponase alfa is safe for your child, tell your doctor if the child has ever had:

• slow heartbeats;

• a heart defect; or

• heart rhythm problems.

Cerliponase alfa is not approved for use by anyone younger than 3 years old.

Contraindications

• Acute intraventricular access device-related complications (e.g., leakage, device failure, device-related infection).1

• Patients with ventriculoperitoneal shunts.1

Warnings/Precautions

Intraventricular Access Device-Related Complications

Cerliponase alfa must be administered using aseptic technique to reduce the risk of infection. Healthcare professionals should inspect the scalp for skin integrity to ensure the intraventricular access device is not compromised prior to each infusion. 1

Cerliponase alfa is contraindicated if there are signs of acute intraventricular access device-related complications (e.g., leakage, device failure or signs of device-related infection such as swelling, erythema of the scalp, extravasation of fluid, or bulging of the scalp around or above the intraventricular access device). In case of intraventricular access device complications, discontinue the cerliponase alfa infusion and refer to the device manufacturer’s labeling for further instructions.1

The signs and symptoms of device-related infections may not be apparent, therefore, CSF samples should routinely be sent for testing to detect subclinical device infections.1

In clinical studies with cerliponase alfa, intraventricular access device-related infections were observed in two patients. In each case, antibiotics were administered, the intraventricular access device was replaced, and the patient continued on cerliponase alfa treatment.1

Material degradation of the intraventricular access device reservoir may occur after approximately 105 perforations of the intraventricular access device. The intraventricular access device may require replacement as soon as, or prior to, 105 administrations of cerliponase alfa, equating to approximately 4.3 years of regular administrations.1

Cardiovascular Adverse Reactions

Monitor vital signs (blood pressure, heart rate) before infusion starts, periodically during infusion, and post-infusion in a healthcare setting. Upon completion of the infusion, clinically assess the patient status. Continued observation may be necessary if clinically indicated.1

Perform electrocardiogram (ECG) monitoring during infusion in patients with a history of bradycardia, conduction disorder, or with structural heart disease, as some patients with CLN2 disease may develop conduction disorders or heart disease. In patients without cardiac abnormalities, regular 12-lead ECG evaluations should be performed every 6 months.1

In the clinical studies, hypotension was reported in 2 (8%) patients, which occurred during or up to eight hours after cerliponase alfa infusion. Patients did not require alteration in treatment, and reactions resolved spontaneously or after intravenous fluid administration.1

Hypersensitivity Reactions

Hypersensitivity reactions have been reported in cerliponase alfa-treated patients during the clinical studies. A total of 11 (46%) patients experienced hypersensitivity reactions during the infusion or within 24 hours of completion of the infusion. The signs and symptoms observed concomitantly with hypersensitivity reactions included pyrexia, vomiting, pleocytosis or irritability. Patients were routinely pre-medicated with antihistamines with or without antipyretics or corticosteroids, prior to infusion of cerliponase alfa.1

Due to the potential for anaphylaxis, appropriate medical support should be readily available when cerliponase alfa is administered. If anaphylaxis occurs, immediately discontinue the infusion and initiate appropriate medical treatment. Observe patients closely during and after the infusion. Inform patients/caregivers of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur.1

The management of hypersensitivity reactions should be based on the severity of the reaction and may include temporarily interrupting the infusion, and/or treatment with antihistamines, antipyretics, and/or corticosteroids. If a severe hypersensitivity reaction occurs, immediately discontinue the infusion and initiate appropriate medical treatment.1

Specific Populations

There are no available data on cerliponase alfa use in pregnant women to inform a drug-associated risk of pregnancy-related outcomes. Animal reproduction studies have not been conducted using cerliponase alfa.1

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.1

There are no data on the presence of cerliponase alfa in human milk, the effects on the breastfed child, or the effects on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of cerliponase alfa to an infant during lactation; therefore, the development and health benefits of breastfeeding should be considered along with the mother’s clinical need for cerliponase alfa and any potential adverse effects on the breastfed infant from cerliponase alfa or from the underlying maternal condition.1

Safety and effectiveness of cerliponase alfa have been established in pediatric patients 3 years of age and older. Pediatric use of cerliponase alfa to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with CLN2 is supported by a nonrandomized, single-arm, dose escalation clinical study with extension in patients with CLN2 disease and compared to untreated patients with CLN2 disease from an independent natural history cohort. Safety and effectiveness in patients less than 3 years of age have not been established.1

Common Adverse Effects

Most common adverse reactions (≥8%) are: pyrexia, ECG abnormalities, decreased CSF protein, vomiting, seizures, hypersensitivity, increased CSF protein, hematoma, headache, irritability, pleocytosis, device-related infection, bradycardia, feeling jittery, and hypotension.1

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Concerns related to adverse effects:

• Cardiovascular adverse reactions: Hypotension has been reported up to 8 hours after the completion of cerliponase alfa infusion; monitor vital signs. Use with caution in patients with a history of bradycardia, conduction disorder, or structural heart disease; monitor EKG during infusion.

• Device-related complications: Complications can occur with intraventricular access devices. Device-related infections have been reported with cerliponase alfa and may be subclinical. Administer using aseptic technique to minimize infection. Monitor access point skin integrity and send CSF samples routinely for signs of infection. Management of infection may include antibiotic treatment and device replacement before resumption of therapy. Monitor the device for signs of leakage or device failure. Material degradation of the intraventricular access device reservoir may occur with prolonged use (≥105 perforations), requiring replacement of the device.

• Hypersensitivity reactions: Hypersensitivity reactions, including pyrexia, vomiting, pleocytosis and irritability, have been reported in patients, during and up to 24 hours after completion of cerliponase alfa infusion. Pretreat with antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes prior to start of infusion.

Other warnings/precautions:

• Appropriate use: Administer cerliponase alfa by FDA-approved infusion pump system via intraventricular implanted catheter access (consult prescribing information for device details); health care providers should be experienced with intraventricular drug administration.

Vital signs (blood pressure, heart rate) prior to start of infusion, periodically during infusion and post-infusion; skin integrity (prior to infusion); routine CSF samples (to detect subclinical device infections); 12-lead EKG every 6 months or during infusion with cardiac abnormalities.

Cerliponase alfa is infused directly in the cerebrospinal fluid through a catheter device that is surgically implanted in the child's head. This device must be in place at least 5 to 7 days before your child gets his or her first dose of cerliponase alfa.

Cerliponase alfa is given using an infusion pump. The medicine enters the body through a catheter placed through the skull and into the brain.

Cerliponase alfa is given only by a certain type of healthcare professional. To prevent infection, cerliponase alfa is given in a sterile medical setting.

This medicine is usually given once every other week. Your child will also receive an infusion of electrolytes after each infusion of cerliponase alfa. The entire procedure will take about 4.5 hours to complete.

About 30 to 60 minutes before each cerliponase alfa infusion, your child will be given medication to prevent certain side effects of this medicine.

Your child's breathing, blood pressure, oxygen levels, and other vital signs will be watched closely during each infusion. The child's heart function may also need to be monitored using an electrocardiograph or ECG (sometimes called an EKG).

In some cases, the child's heart function should be checked every 6 months. Be sure to keep all appointments with your child's doctor.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Call your doctor for instructions if you miss an appointment for your child's cerliponase alfa infusion.

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 doctor or get medical help right away if you have 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 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.
• A heartbeat that does not feel normal.
• Fast or slow heartbeat.
• Very bad dizziness or passing out.
• Seizures.
• Feeling irritable.
• Feeling jittery.
• Throwing up.

Data not available

Administration advice:
-Administered into the cerebrospinal fluid (CSF) by intraventricular infusion via a surgically implanted reservoir and catheter (intraventricular access device).
-Must only be administered by the intraventricular route, using the provided administration kit; each vial of this drug and electrolytes is for single use only.
-Each infusion consists of 10 mL of this drug followed by 2 mL of intraventricular electrolytes. administered using an infusion set with a 0.2 micron inline filter.
-Infuse both this drug and electrolytes at an infusion rate of 2.5 mL/hr; complete infusion, including required electrolytes, is about 4.5 hours.
-The Codman(R) HOLTER RICKHAM Reservoirs should be used with the Codman(R) Ventricular Catheter.
-To be administered with the B Braun Perfusor(R) Space Infusion System; consult the manufacturer product information for additional information.
-The intraventricular access device must be implanted prior to the first infusion and the first dose administered at least 5 to 7 days after device implantation.
-Aseptic technique must be strictly enforced during preparation and administration.
-To be administered by, or under the direction of a physician knowledgeable in intraventricular administration.
-The manufacturer product information should be consulted for direction in the intraventricular infusion procedure.

Storage requirements:
-Store upright in a freezer (-25C to -15C [-13F to 5F]) in original carton to protect from light.
-Store the administration kit, including vials containing electrolytes, in original carton separately; do not freeze.

Reconstitution/preparation techniques:
-The manufacturer product information should be consulted.

Monitoring:
-Cardiovascular: Monitor vital signs (e.g., blood pressure, heart rate) prior to infusion, periodically during infusion, and post-infusion in a healthcare setting. Perform ECG monitoring during infusion in patients with a history of bradycardia, conduction disorder, or with structural heart disease; regular 12-lead ECG evaluations should occur every 6 months in patients without cardiac abnormalities.
-Hypersensitivity: Observe patients closely during and after infusion for signs/symptoms off allergic reactions, including anaphylaxis.

Patient advice:
-Immediately contact your healthcare provider if any signs of infection occur.
-Immediately contact your healthcare provider if hypotension and/or bradycardia occur during or following infusion.
-Seek medical attention if any signs/symptoms of a hypersensitivity reaction (e.g., fever, vomiting, irritability) or signs/symptoms of anaphylaxis occur.