cerliponase alfa (Rx)

>10%

Pyrexia (71%)

ECG abnormalities (71%)

Decreased CSF protein (71%)

Vomiting (63%)

Seizures (50%)

Hypersensitivity (46%)

Increased CSF protein (21%)

Hematoma (21%)

Headache (17%)

Irritability (17%)

Pleocytosis (17%)

1-10%

Device-related infection (8%)

Bradycardia (8%)

Feeling jittery (8%)

Hypotension (8%)

Postmarketing Reports

Bacterial meningitis

Immune system disorders: Anaphylactic reaction characterized by acute pyrexia, respiratory distress (bronchospasm, hypoxemia, perioral cyanosis), tachycardia, hypotension, diarrhea, and rash

Contraindications

Any sign or symptom of acute, unresolved localized infection on or around the device insertion site (e.g. cellulitis or abscess); or suspected or confirmed CNS infection (e.g. cloudy CSF or positive CSF gram stain, or meningitis)

Any acute intraventricular access device-related complication (e.g., leakage, extravasation of fluid, or device failure)

Patients with ventriculoperitoneal shunts

Cautions

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 (see Administration)

Monitor vital signs before infusion starts, periodically during infusion, and postinfusion in a healthcare setting

Perform 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

Hypersensitivity reactions

• Hypersensitivity reactions, including anaphylaxis, reported during infusion or within 24 hr of completion; observe patient during and after infusion; inform caregivers of signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if these occur
• Consider risks and benefits of readministration following anaphylactic reaction; if decision is made to readminister therapy after occurrence of anaphylaxis, ensure appropriately trained personnel and equipment for emergency resuscitation (including epinephrine and other emergency medicines) are readily available during infusion; initiate subsequent infusion at approximately one-half initial infusion rate at which anaphylactic reaction occurred

Intraventricular access complications

• Bacterial meningitis requiring antibiotic treatment and removal of device reported during postmarketing use; signs and symptoms of infections may not be readily apparent in patients with CLN2 disease; therapy should be administered by, or under direction of, physician experienced in intraventricular administration to reduce risk of infectious complications
• Obtain a sample of CSF for cell count and culture prior to each infusion and when clinically indicated
• Do not administer therapy if there are localized signs of infection on or around device insertion site, such as erythema, tenderness, or discharge or suspected or confirmed CNS infection (e.g. cloudy CSF or positive CSF gram stain, or meningitis)
• Healthcare providers should be vigilant for development of signs and symptoms of infection, including meningitis, during treatment and monitor device insertion site for signs of infection
• Consult a neurosurgeon for any complications with implanted device; in case of device-related complication, discontinue infusion and refer to device labeling for further instructions

Pregnancy

There are no available data on use in pregnant women to inform a drug-associated risk of pregnancy-related outcomes

Lactation

Unknown if distributed in human breast milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant form of human tripeptidyl peptidase (TPP-1) that provides enzyme replacement therapy; this results in a restored breakdown of the lysosomal storage materials that cause CLN2 disease

CLN2 late infantile disease is caused by a deficiency in the TPP-1 enzyme, a lysosomal enzyme that cleaves peptides into amino acids; TPP-1 deficiency causes abnormal storage of proteins and lipids in neurons and other cells, resulting in impaired cellular function

Pharmacokinetics

Expected to be degraded through peptide hydrolysis

CSF

• Tmax: 4.3-4.5 hr
• Cmax: 1260-1630 mcg/mL
• AUC: 9290-12,400 mcg·hr/mL
• Vd: 186-245 mL
• Distribution half-life: 2.5-7.7 hr

Plasma

• Tmax: 12-12.3 hr
• Cmax: 1-1.9 mcg/mL
• AUC: 9.5-40.1 mcg·hr/mL

Intraventricular Preparation

Aseptic technique must be strictly observed during preparation and administration

Thaw cerliponase alfa and intraventricular electrolytes injection vials at room temperature for ~60 minutes

Do not thaw or warm vials any other way

Do not shake vials

Condensation will occur during thawing period

Do not refreeze vials or freeze syringes containing the drug or electrolyte solutions

Cerliponase alfa is a clear to slightly opalescent and colorless to pale yellow solution

Intraventricular electrolytes is a clear to colorless solution

Do not use if the solutions are discolored or if there is other foreign particulate matter in the solutions

Cerliponase alfa vials may occasionally contain thin translucent fibers or opaque particles; these naturally occurring particles are cerliponase alfa and are removed via the 0.2 micron inline filter without having a detectable effect on the purity or potency

Intraventricular electrolytes may contain particles, which appear during the thaw period; however, these dissolve when the solution reaches room temperature

Do not dilute cerliponase alfa or mix with any other drug

Administration kit includes

• Two 20-mL syringes
• Two syringe needles (21 ga, 25.4 mm)
• One extension line
• One infusion set with 0.2 micron inline filter
• One port needle (22 ga, 16 mm)

Intraventricular Administration

Administered by, or under the direction of, a physician knowledgeable in intraventricular administration

Prior to each infusion inspect scalp for signs of intraventricular access device leakage, failure or potential infection

Prior to each infusion and when clinically indicated, obtain a sample of CSF for cell count and culture

Administered into the CSF by infusion via a surgically implanted reservoir and catheter (intraventricular access device); intended to be administered via the Codman HOLTER RICKHAM Reservoirs (Part Numbers: 82-1625, 82-1621, 82-1616) with the Codman Ventricular Catheter (Part Number: 82-1650)

The intraventricular access device must be implanted prior to the first infusion

Intended to be administered with the B Braun Perfusor® Space Infusion Pump System (Product Code: 8713030). If an alternative pump must be used, the essential performance requirements for a syringe pump used to deliver Brineura are as follows

Delivery rate of 2.5 mL/hr with delivery accuracy of +/- 1 mL/hr

Compatible with 20 mL syringes provided in the Administration Kit for use with cerliponase alfa)

Occlusion alarm setting to ≤ 281 mm Hg

Cleared for intraventricular route of administratio

Administer ceioand the IV electrolytes

It is recommended that the first dose be administered at least 5-7 days after device implantation

Each infusion consist of 10 mL cerliponase alfa followed by 2 mL of intraventricular electrolytes using an infusion set with a 0.2 micron line filter (provided in kit)

Infusion rate: cerlionase alfa 2.5 mL/hr and electrolytes 2.5 mL/hr; total infusion time is ~4.5 hr

The intraventricular electrolytes are used to flush the infusion line, port needle, and intraventricular access device in order to fully administer the cerliponase alfa dose and to maintain patency of the intraventricular access device

See prescribing information for diagram of intraventricular infusion procedure

Administer by B Braun Perfusor Space Infusion Pump System

• The essential performance requirement for this syringe pump used to deliver cerliponase alfa are as follows

  • Delivery rate of 2.5 mL/hr with accuracy of +/- 1 mL/hr
  • Compatible with 20-mL syringes provided in the administration kit
  • Occlusion alarm setting to ≤281 mmHg

Storage

Store cerliponase alfa injection and intraventricular electrolytes injection upright in freezer (-25°C to -15°C) in original carton to protect from light

Administration kit: Store in original carton separately from cerliponase alfa (do not freeze)

Thawed product

• Use thawed cerliponase alfa and intraventricular electrolytes immediately
• If not used immediately, store unopened vials in the refrigerator at 2-8°C and use within 24 hr

Thawed product in syringes

• Use product held in labeled syringes immediately
• If not used immediately, store product held in labeled syringes in the refrigerator at 2-8°C up to 4 hr prior to infusion