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Brineura cerliponase alfa Kit — NDC 68135-0811-02 package photo
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Brineura cerliponase alfa Kit — NDC 68135-811-02 (Billing 68135-0811-02)

by BioMarin Pharmaceutical Inc. · 1 KIT in 1 CARTON * 5 mL in 1 VIAL, GLASS * 5 mL in 1 VIAL, GLASS

This is a package of Brineura cerliponase alfa Kit from BioMarin Pharmaceutical Inc., marketed since Apr 2017 and currently FDA-listed. It is this product's only package size.

NDC 68135-0811-02
🏷️ FDA NDC (as labeled) 68135-811-02 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 68135-811-02 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
68135 labeler · 811 product · 02 package
Package marketed since
Apr 27, 2017
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 6813581102 2
Medicaid fills, this package
72 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68135-811-02
Product NDC 68135-811
11-digit billing NDC 68135081102
NCPDP billing unit EA — each (per item)
RxCUI 1922453, 1922458
Application # BLA761052
SPL Set ID 485ab3c5-0359-4878-872f-2fe1e7df4047
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-04-27
Dosage form KIT
Biologic (Purple Book) 351(a)

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 30909020106420
GPI class Brineura
GCN Seq No 077434
GCN 43455
HICL code 044258
Ingredient (HICL) Cerliponase Alfa
HIC1 code Z
Therapeutic class — broad (HIC1) Body As A Whole
HIC2 code Z1
Therapeutic class — intermediate (HIC2) Positive Effects On Wide-Spread Tissue
HIC3 code Z1U
Therapeutic class — specific (HIC3) Metabolic Disease Enzyme Replacement, Batten Disea
AHFS code 44:00.00.00
AHFS class Enzymes
FDB label name BRINEURA 2X150MG/5ML-ELYTE KIT
FDB brand name Brineura
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 077434
  • GCN: 43455
  • GPI-14 (Medi-Span): 30909020106420
  • HICL (First Databank): 044258
  • AHFS class code: 44:00.00.00
  • RxCUI (RxNorm): 1922453
Why two NDCs? The FDA registers this code as 68135-811-02 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 68135-0811-02. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Hydrolytic Lysosomal N-terminal Tripeptidyl Peptidase class.

Pharmacologic class Hydrolytic Lysosomal N-terminal Tripeptidyl Peptidase
Drug family (ATC) Enzymes
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name BRINEURA 2X150MG/5ML-ELYTE KIT Ingredient Cerliponase Alfa
📖 What it is MedlinePlus · NLM

Cerliponase alfa is used to slow the loss of being able to crawl or walk in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease; an inherited disease of the nervous system), also known as tripeptidyl peptidase 1 (TPP1) deficiency. Cerliponase alfa is in a class of medications called enzymes. It works by replacing the lack of TPP1 in the nervous system.

Read the full MedlinePlus article ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $13,391.79 —
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
68135-0811-02 You're viewing this Main listing 1 KIT in 1 CARTON * 5 mL in 1 VIAL, GLASS * 5 mL in 1 VIAL, GLASS 2017-04-27 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Brineurathis 68135-0811-02 BioMarin 1 kit — — FDA listed —
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & biosimilar status

🏛️
2017
First FDA approval
Apr 2017
📍
2026
Currently FDA-listed
9 years listed
🛡️
2029
Latest patent/protection listed
not a guaranteed launch date
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Apr 2029. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.
📅 FDA approved Apr 27, 2017 ⏳ ~2.6 yr to latest listed protection

Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Brineuracerliponase alfa
🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2017 2019 2021 2023 2025 2027 2029
Today
LOE
Biologic patent Exclusivity
🏛️Reference-product exclusivity
A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.
🧪Listed biologic patents
Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.
🔁Interchangeability
An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.
🛈 What do these terms mean?
Biologic patent
A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
Reference-product exclusivity
A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
Interchangeable exclusivity
The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
Earliest biosimilar (LOE)
The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.

Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.

FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateApr 27, 2029
Common questions
Is there a biosimilar for BRINEURA 2X150MG/5ML-ELYTE KIT?
No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.
Why do different websites show different biosimilar dates?
Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.
Can a biosimilar launch before the last patent expires?
Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.
What does “current Purple Book estimate” mean?
It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.
What does “FDA listed” mean?
It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.
Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

A current SPL was checked, but it does not contain a structured or narrative inactive-ingredient list for this product. This does not mean the product has no inactive ingredients.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerBioMarin Pharmaceutical Inc.
FDA applicationBLA761052 (BLA)
Labeler code68135
First marketedApr 2017
Product typeHuman Prescription Drug
Portfolio17 products on file

More NDCs from BioMarin Pharmaceutical Inc. labeler code 68135

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 178 words ▾

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment.

If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue BRINEURA and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ]. WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

( 5.1 ) Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. ( 5.1 ) If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue BRINEURA and immediately initiate appropriate medical treatment, including use of epinephrine. ( 5.1 )

🎯 Indications and Usage 69 words ▾

1 INDICATIONS AND USAGE BRINEURA is indicated to slow the loss of ambulation in pediatric patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency. BRINEURA is a hydrolytic lysosomal N-terminal tripeptidyl peptidase indicated to slow the loss of ambulation in pediatric patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. ( 2.1 ) BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration. ( 2.1 ) Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended.

( 2.1 ) Prior to each infusion, inspect the scalp for signs of intraventricular access device reservoir leakage, failure, or potential infection. ( 2.1 ) Recommended BRINEURA dosage is 300 mg administered once every other week as an intraventricular infusion. In patients less than 2 years of age, lower doses are recommended.

( 2.2 ) Dosing is not recommended in patients less than 37 weeks post-menstrual age or those weighing less than 2.5 kg. ( 2.2 ) See the full prescribing information for dosage modifications due to hypersensitivity reactions. ( 2.3 ) See the full prescribing information for preparation and administration instructions.

( 2.4 , 2.6 )

2.1Recommendations Prior to BRINEURA Treatment Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1) ] . BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration via a surgically implanted intraventricular access device system which consists of the reservoir and catheter components [see Dosage and Administration (2.6) ] .

Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion [see Warnings and Precautions (5.1 , 5.5) ] . Aseptic technique must be strictly observed during preparation and administration [see Dosage and Administration (2.6) ] . Prior to each infusion of BRINEURA, inspect the scalp for signs of intraventricular access device reservoir leakage, failure or potential infection [see Warnings and Precautions (5.2 , 5.3) ] .

Prior to each infusion of BRINEURA and when clinically indicated, obtain a sample of CSF for cell count and culture [see Warnings and Precautions (5.2) ] . Replace the intraventricular access device reservoir prior to 4 years of single-puncture administrations [see Warnings and Precautions (5.3) ].

2.2Recommended Dosage and Administration The recommended dosage of BRINEURA in pediatric patients is provided in Table 1. The dose is administered once every other week by intraventricular infusion. BRINEURA is not recommended in patients less than 37 weeks post-menstrual age (gestational age at birth plus post-natal age) or those weighing less than 2.5 kg [see Use in Specific Populations (8.4) ].

Administer BRINEURA first followed by infusion of the Intraventricular Electrolytes. The complete BRINEURA infusion, including the required infusion of Intraventricular Electrolytes, is approximately 2 to 4.5 hours, depending on the dose and volume administered. See Table 1 for the appropriate volume and infusion rate.

For volumes that are not whole numbers, see Dosage and Administration (2.6) . Table 1: BRINEURA Dose, Volume, and Infusion Rate by Age Age groups BRINEURA dose administered every other week Volume of BRINEURA solution Infusion rate Birth to < 6 months 100 mg 3.3 mL 1.25 mL/hr 6 months to < 1 year 150 mg 5 mL 2.5 mL/hr 1 year to < 2 years 200 mg (first 4 doses) 6.7 mL (first 4 doses) 2.5 mL/hr 300 mg (subsequent doses) 10 mL (subsequent doses) 2 years and older 300 mg 10 mL 2.5 mL/hr Missed Dose If one or more doses are missed, restart BRINEURA treatment as soon as possible, maintaining the 2-week interval between infusions thereafter.

2.3Administration Modificati… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 85 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: BRINEURA 150 mg/5 mL (30 mg/mL) solution, two single-dose vials per carton co-packaged with Intraventricular Electrolytes Injection 5 mL in a single-dose vial. BRINEURA is a clear to slightly opalescent and colorless to pale yellow solution. Intraventricular Electrolytes is a clear to colorless solution [see How Supplied/Storage and Handling (16) ] .

Injection: BRINEURA 150 mg/5 mL (30 mg/mL) solution, two single-dose vials per carton co-packaged with Intraventricular Electrolytes Injection 5 mL in a single-dose vial. ( 3 )

⛔ Contraindications 137 words ▾

4 CONTRAINDICATIONS BRINEURA is contraindicated in patients with: 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) [see Warnings and Precautions (5.2) ] . any acute intraventricular access device-related complication (e.g., leakage, extravasation of fluid, or device failure) [see Warnings and Precautions (5.3) ]. ventriculoperitoneal shunts.

Any sign or symptom of acute or 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). ( 4 ) Any acute intraventricular access device-related complication (e.g., leakage, extravasation of fluid, or device failure). ( 4 ) Patients with ventriculoperitoneal shunts.

( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Meningitis and Other Intraventricular Access Device-Related Infections : Monitor the device insertion site for signs of infection. ( 4 , 5.2 ) Intraventricular Access Device-Related Complications : Consult a neurosurgeon for any complications with the implanted device. In case of device-related complication, discontinue the infusion and refer to the device labeling for further instructions.

( 4 , 5.3 ) Cardiovascular Adverse Reactions : Monitor vital signs before, during, and post-infusion. Monitor Electrocardiogram (ECG) in patients with a history of bradycardia, conduction disorder, or with structural heart disease, during the infusion. In patients without cardiac abnormalities, perform regular 12-lead ECG evaluations every 6 months.

( 2.5 , 5.4 ) Infusion-Associated Reactions (IARs) : If an IAR occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administering antihistamines and/or antipyretics may ameliorate the symptoms. ( 5.5 )

5.1Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions including anaphylaxis have been reported in patients treated with enzyme replacement therapies, including BRINEURA . BRINEURA-treated patients have had these reactions occur in clinical studies and postmarketing use [see Adverse Reactions (6) ] . In clinical Trial 1 and Trial 2 to 96 weeks, a total of 11 of 24 (46%) patients experienced hypersensitivity reactions during the infusion or within 24 hours of completion of the infusion.

Patients in clinical trials were routinely pre-medicated with antihistamines with or without antipyretics or corticosteroids, prior to infusion of BRINEURA. During postmarketing use, anaphylactic reactions occurred during or within several hours of BRINEURA infusion. Epinephrine was administered in these patients, and they received subsequent BRINEURA infusions without recurrence of anaphylaxis.

In Trial 3, hypersensitivity reactions were reported in 5 of 8 (63 %) patients less than 3 years of age at baseline as compared to 0 of 6 patients ≥ 3 years of age at baseline [see Adverse Reactions (6.1) ] . Of the reported hypersensitivity reactions, a single anaphylactic reaction occurred in a subject < 3 years of age. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate BRINERUA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion.

Observe patients closely during and after the infusion. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue BRINEURA and immediately initiate appropriate medical treatment including use of epinephrine. Inform patients and caregivers of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.

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. Consider the risks and benefits of readministration of BRINEURA following an anaphylactic reaction. If the decision is made to readminister BRINEURA after the 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 the initial infusion rate at which the anaphylactic reaction occurred.

5.2Meningitis and Other Intraven… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Meningitis and Other Intraventricular Access Device-Related Infections [see Warnings and Precautions (5.2) ] Intraventricular Access Device-Related Complications [see Warnings and Precautions (5.3) ] Cardiovascular Adverse Reactions [see Warnings and Precautions (5.4) ] Infusion-Associated Reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions (≥8%) are: pyrexia, ECG abnormalities, decreased CSF protein, vomiting, seizures, device-related complications, hypersensitivity, increased CSF protein, hematoma, headache, irritability, pleocytosis, device-related infections, bradycardia, feeling jittery, and hypotension.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BioMarin at 1-866-906-6100 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Trial 1 and Trial 2 The safety of BRINEURA was evaluated in 24 patients with CLN2 disease who received at least one 300 mg dose of BRINEURA given by intraventricular infusion in a clinical trial with extension (Trials 1 and 2) of up to 161 weeks [see Clinical Studies (14) ] .

Table 2 summarizes the most common adverse reactions that occurred in BRINEURA-treated patients through 96 weeks. Table 2: Adverse Reactions Reported in ≥ 8% of Symptomatic Pediatric Patients with CLN2 Disease in BRINEURA Trial 1 and Trial 2 at Week 96 Adverse Reaction Patients Treated with BRINEURA n=24 (%) Increased body temperature Increased body temperature includes: increased body temperature and pyrexia 17 (71) ECG abnormalities ECG abnormalities include: non-specific repolarization abnormality, notched QRS, ST segment elevation, biphasic T wave abnormality, supraventricular extrasystoles, bradycardia, sinus tachycardia, and intraventricular conduction delay 17 (71) Decreased CSF protein 17 (71) Vomiting 15 (63) Seizures Seizures include: atonic, generalized tonic-clonic, focal, and absence 12 (50) Device-related complications Device-related complications include device-related infection, delivery system-related complications (needle issues, device leakage, device malfunction, device difficult to use, medical device site irritation, device breakage, etc.) and pleocytosis.

12 (50) Hypersensitivity Hypersensitivity includes only hypersensitivity [see Warnings and Precautions (5.4) ] 9 (38) Increased CSF protein 5 (21) Hematoma 5 (21) Headache 4 (17) Irritability 4 (17) Pleocytosis 4 (17) Device-related infections Device-related infections include: Propionibacterium acnes and Staphylococcus epidermidis 2 (8) Bradycardia 2 (8) Feeling jittery 2 (8) Hypotension 2 (8) Description of Selected Adverse Reactions from Trial 1 and Trial 2 at 96 weeks Seizures Seizures were reported in 12 of 24 (50%) patients.

The seizure types reported include atonic, generalized tonic-clonic, focal, and absence. Seizures were managed with standard anti-convulsive therapies and did not result in discontinuation of BRINEURA treatment. Device-Related Complications Adverse reactions related to the device were observed in 12 of 24 (50%) of patients.

Device-related adverse reactions include infection, delivery system-related complications, and pleocytosis. Nine out of 24 patients (38%) experienced adverse reactions, which involved complications of the non-implanted delivery system components. Four out of 24 patients (16%) had device-related adverse reactions, which required medical intervention, including two patients (8%) with intraventricular access device-related CNS infections, and one patient (4%) each with leakage of the intraventricular ac… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~1 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are no available data on BRINEURA use in pregnant women to inform a drug-associated risk of pregnancy-related outcomes. Animal reproduction studies have not been conducted using cerliponase alfa. 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.

8.2Lactation Risk Summary 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 BRINEURA to an infant during lactation; therefore, the development and health benefits of breastfeeding should be considered along with the mother's clinical need for BRINEURA and any potential adverse effects on the breastfed infant from BRINEURA or from the underlying maternal condition.

8.4Pediatric Use The safety and effectiveness of BRINEURA have been established to slow the loss of ambulation in pediatric patients with CLN2 disease and the information on this use is discussed throughout the labeling. BRINEURA is not recommended for use in patients less than 37 weeks post-menstrual age (gestational age at birth plus post-natal age) or those weighing less than 2.5 kg due to physiologic immaturity which may increase risk of serious and clinically significant adverse reactions observed with BRINEURA [see Warnings and Precautions (5) ] .

Patients less than 3 years of age may be at increased risk for developing hypersensitivity reactions with BRINEURA use compared to patients 3 years of age and older [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].

🤰 Pregnancy 91 words ▾

8.1Pregnancy Risk Summary There are no available data on BRINEURA use in pregnant women to inform a drug-associated risk of pregnancy-related outcomes. Animal reproduction studies have not been conducted using cerliponase alfa. 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.

🧒 Pediatric Use 126 words ▾

8.4Pediatric Use The safety and effectiveness of BRINEURA have been established to slow the loss of ambulation in pediatric patients with CLN2 disease and the information on this use is discussed throughout the labeling. BRINEURA is not recommended for use in patients less than 37 weeks post-menstrual age (gestational age at birth plus post-natal age) or those weighing less than 2.5 kg due to physiologic immaturity which may increase risk of serious and clinically significant adverse reactions observed with BRINEURA [see Warnings and Precautions (5) ] .

Patients less than 3 years of age may be at increased risk for developing hypersensitivity reactions with BRINEURA use compared to patients 3 years of age and older [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism 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.

12.2Pharmacodynamics No formal pharmacodynamic studies have been conducted with cerliponase alfa.

12.3Pharmacokinetics Patients 3 years of age and older The pharmacokinetics of cerliponase alfa were evaluated in patients with CLN2 disease who received intraventricular infusions of 30 mg (0.1 times the maximum approved recommended dosage), 100 mg (approximately 0.3 times the maximum approved recommended dosage), and 300 mg over approximately 4.5 hours once every other week. Cerliponase alfa CSF exposure following the initial single dose administration of BRINEURA increased less than proportionally across doses of 30 mg, 100 mg, and 300 mg.

There was no apparent accumulation of cerliponase alfa in CSF or plasma when BRINEURA was administered at a dose of 300 mg once every other week. Cerliponase alfa pharmacokinetics have high inter-subject and intra-subject variability. Following intraventricular infusions of 300 mg of BRINEURA at Day 1, Week 5, and Week 13, the pharmacokinetic parameters in CSF and plasma were assessed in 14 patients and are summarized in Table 4.

Table 4: Pharmacokinetic Parameters of Cerliponase Alfa Following Intraventricular Infusion (approximately 4.5 hours in duration) of BRINEURA 300 mg Every Two Weeks in Patients ≥ 3 years Parameter Median [Min, Max] Day 1 Week 5 Week 13 N 13 14 13 T max T max expressed as time since start of ~4.5 hour infusion. , hr 4.5 [4.3, 5.8] 4.3 [3.8, 4.5] 4.3 [4.0, 4.5] C max , mcg/mL 1260 [359, 4380] 1630 [376, 4670] 1390 [1110, 2340] CSF AUC 0-t , mcg-hr/mL 9290 [3660, 19000] 12400 [4620, 26200] 10500 [7000, 18200] V ss , mL 245 [78.4, 909] 196 [85.4, 665] 186 [131, 257] CL, mL/hr 32.3 [15.8, 81.9] 24.2 [11.4, 64.9] 28.7 [16.5, 42.9] t 1/2 , hr 6.2 [5.5, 16.3] 7.4 [3.3, 9.5] 7.7 [5.1, 9.4] N 12 12 9 Plasma V ss , CL, and t 1/2 were not estimated due to insufficient plasma pharmacokinetic data T max , hr 12.0 [4.3, 24.5] 12.0 [7.5, 24.2] 12.3 [4.3, 75.9] C max , mcg/mL 1.3 [0.2, 3.9] 1.9 [0.2, 4.3] 1.0 [0.03, 2.6] AUC 0-t , mcg-hr/mL 16.2 [1.1, 69.9] 40.1 [11.1, 78.9] 9.5 [0.2, 51.6] N 11 12 9 CSF/Plasma Ratio C max 1200 [305, 4530] 809 [202, 9370] 1320 [541, 51200] AUC 0-t 393 [115, 1910] 340 [126, 1780] 1330 [167, 38900] The estimated CSF volume of distribution of cerliponase alfa following intraventricular infusion of 300 mg of BRINEURA (median V ss = 245 mL) exceeds the typical CSF volume (100 mL).

Pediatric patients less than 3 years Pediatric CLN2 patients ages 1 to < 2 years (n=2) and 2 to < 3 years (n=6) were administered cerliponase alfa according to the recommended dosing regimen based on age for up to 144 weeks. CSF exposure with 300 mg cerliponase alfa was within the range characterized to be safe and effective in pivotal Trial 1. Plasma exposure in younger patients trended higher than the range characterized in the pivotal study.

The pharmacokinetic parameters summarized by age at time of visit and dose are shown in Table 5. Table 5: Pharmacokinetic Parameters of Cerliponase Alfa by Age at Visit and Dose Following Intraventricular Infusion of BRINEURA Every Two Weeks in Pediatric Patients < 3 years Age at Visit Dose (mg) Parameter Median [Min, Max] 1… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 115 words ▾

12.1Mechanism 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.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING BRINEURA is supplied as a sterile, clear to slightly opalescent and colorless to pale yellow solution for intraventricular infusion and Intraventricular Electrolytes Injection is supplied as a clear to colorless solution for intraventricular infusion; both are included in package 1 of 2. The Administration Kit for use with BRINEURA is supplied separately as package 2 of 2 [see Dosage and Administration (2.4) ] . Package 1 of 2 Each BRINEURA (cerliponase alfa) Injection vial has a green flip-off cap (plastic) and contains 150 mg cerliponase alfa per 5 mL (30 mg/mL).

Each Intraventricular Electrolytes Injection vial has a yellow flip-off cap (plastic) and contains 5 mL of solution. Contents of Package 1 NDC Number BRINEURA (cerliponase alfa) Injection (2 vials of 150 mg/5 mL) Intraventricular Electrolytes Injection (1 vial, 5 mL) 68135-811-02 Package 2 of 2 The Administration Kit for use with BRINEURA is supplied separately and contains the following single-use, sterile infusion components: Two 20-mL syringes Two syringe needles (21 G, 25.4 mm) One extension line One infusion set with 0.2 micron inline filter One port needle (22 G, 16 mm) Storage BRINEURA (cerliponase alfa) Injection and Intraventricular Electrolytes Injection: Store upright in a freezer (-25°C to -15°C) in original carton to protect from light.

Administration Kit for use with BRINEURA: Store in original carton separately from BRINEURA. Do not freeze.

📦 Storage and Handling 40 words ▾

Storage BRINEURA (cerliponase alfa) Injection and Intraventricular Electrolytes Injection: Store upright in a freezer (-25°C to -15°C) in original carton to protect from light. Administration Kit for use with BRINEURA: Store in original carton separately from BRINEURA. Do not freeze.

📋 Description ~1 min read ▾

11 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.

💬 Information for Patients 169 words ▾

17 PATIENT COUNSELING INFORMATION Hypersensitivity Reactions Including Anaphylaxis and Infusion-Associated Reactions (IARs) Advise patients and caregivers that life-threatening hypersensitivity reactions, including anaphylaxis, and IARs may occur with BRINEURA treatment. Advise patients and caregivers that anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Inform patients and caregivers of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis, and IARs and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1 , 5.5) ] .

Intraventricular Access Device-Related Infections Advise patients and caregivers of the risk of device-related infections, including meningitis. Familiarize them with the signs and symptoms of these infections and instruct them to immediately contact their healthcare provider if an infection is suspected [see Warnings and Precautions (5.2) ] . Cardiovascular Adverse Reactions Advise patients and caregivers that hypotension and/or bradycardia may occur during and following the infusion of BRINEURA.

Instruct patients immediately to contact their healthcare provider if these reactions occur [see Warnings and Precautions (5.4) ].

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Patients 3 years of age and older The pharmacokinetics of cerliponase alfa were evaluated in patients with CLN2 disease who received intraventricular infusions of 30 mg (0.1 times the maximum approved recommended dosage), 100 mg (approximately 0.3 times the maximum approved recommended dosage), and 300 mg over approximately 4.5 hours once every other week. Cerliponase alfa CSF exposure following the initial single dose administration of BRINEURA increased less than proportionally across doses of 30 mg, 100 mg, and 300 mg.

There was no apparent accumulation of cerliponase alfa in CSF or plasma when BRINEURA was administered at a dose of 300 mg once every other week. Cerliponase alfa pharmacokinetics have high inter-subject and intra-subject variability. Following intraventricular infusions of 300 mg of BRINEURA at Day 1, Week 5, and Week 13, the pharmacokinetic parameters in CSF and plasma were assessed in 14 patients and are summarized in Table 4.

Table 4: Pharmacokinetic Parameters of Cerliponase Alfa Following Intraventricular Infusion (approximately 4.5 hours in duration) of BRINEURA 300 mg Every Two Weeks in Patients ≥ 3 years Parameter Median [Min, Max] Day 1 Week 5 Week 13 N 13 14 13 T max T max expressed as time since start of ~4.5 hour infusion. , hr 4.5 [4.3, 5.8] 4.3 [3.8, 4.5] 4.3 [4.0, 4.5] C max , mcg/mL 1260 [359, 4380] 1630 [376, 4670] 1390 [1110, 2340] CSF AUC 0-t , mcg-hr/mL 9290 [3660, 19000] 12400 [4620, 26200] 10500 [7000, 18200] V ss , mL 245 [78.4, 909] 196 [85.4, 665] 186 [131, 257] CL, mL/hr 32.3 [15.8, 81.9] 24.2 [11.4, 64.9] 28.7 [16.5, 42.9] t 1/2 , hr 6.2 [5.5, 16.3] 7.4 [3.3, 9.5] 7.7 [5.1, 9.4] N 12 12 9 Plasma V ss , CL, and t 1/2 were not estimated due to insufficient plasma pharmacokinetic data T max , hr 12.0 [4.3, 24.5] 12.0 [7.5, 24.2] 12.3 [4.3, 75.9] C max , mcg/mL 1.3 [0.2, 3.9] 1.9 [0.2, 4.3] 1.0 [0.03, 2.6] AUC 0-t , mcg-hr/mL 16.2 [1.1, 69.9] 40.1 [11.1, 78.9] 9.5 [0.2, 51.6] N 11 12 9 CSF/Plasma Ratio C max 1200 [305, 4530] 809 [202, 9370] 1320 [541, 51200] AUC 0-t 393 [115, 1910] 340 [126, 1780] 1330 [167, 38900] The estimated CSF volume of distribution of cerliponase alfa following intraventricular infusion of 300 mg of BRINEURA (median V ss = 245 mL) exceeds the typical CSF volume (100 mL).

Pediatric patients less than 3 years Pediatric CLN2 patients ages 1 to < 2 years (n=2) and 2 to < 3 years (n=6) were administered cerliponase alfa according to the recommended dosing regimen based on age for up to 144 weeks. CSF exposure with 300 mg cerliponase alfa was within the range characterized to be safe and effective in pivotal Trial 1. Plasma exposure in younger patients trended higher than the range characterized in the pivotal study.

The pharmacokinetic parameters summarized by age at time of visit and dose are shown in Table 5. Table 5: Pharmacokinetic Parameters of Cerliponase Alfa by Age at Visit and Dose Following Intraventricular Infusion of BRINEURA Every Two Weeks in Pediatric Patients < 3 years Age at Visit Dose (mg) Parameter Median [Min, Max] 1 to < 2 years 200 CSF N 3 C max , mcg/mL 511 [163, 987] AUC 0-t , mcg-hr/mL 2720 [1100, 5050] Plasma N 2 C max , mcg/mL 10.4 [9.46, 11.3] AUC 0-t , mcg-hr/mL 91.8 [72.7, 111] 300 CSF N 2 C max , mcg/mL 566 [496, 636] AUC 0-t , mcg-hr/mL 8030 [8030, 8030] N=1 due to less than 3 evaluable datapoints for determination of AUC 0-t Plasma N 2 C max , mcg/mL 14.1 [11.2, 17.0] AUC 0-t , mcg-hr/mL 145 [82.7, 206] 2 to < 3 years 300 CSF N 6 C max , mcg/mL 896 [508, 1790] AUC 0-t , mcg-hr/mL 4100 [2380, 6720] N=5 due to less than 3 evaluable datapoints for determination of AUC 0-t Plasma N 6 C max , mcg/mL 14.9 [9.08, 35.3] AUC 0-t , mcg-hr/mL 163 [91.5, 320] Cerliponase alfa is a protein and is expected to be degraded through peptide hydrolysis.

🧬 Pharmacodynamics 12 words ▾

12.2Pharmacodynamics No formal pharmacodynamic studies have been conducted with cerliponase alfa.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of BRINEURA was assessed over 96 weeks in a non-randomized single-arm dose escalation clinical study with extension in symptomatic pediatric patients with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, confirmed by TPP1 deficiency. BRINEURA-treated patients were compared to untreated patients from a natural history cohort. The Motor domain of a CLN2 Clinical Rating Scale was used to assess disease progression.

Scores ranged from 3 (grossly normal) to 0 (profoundly impaired) with unit decrements representing milestone events in the loss of motor function (ability to walk or crawl). Due to the inability to establish comparability for the CLN2 Language domain ratings between the clinical study with extension and the natural history cohort, efficacy of BRINEURA for the Language domain cannot be established. Twenty-four patients, aged 3 to 8 years were enrolled in the BRINEURA single-arm clinical study (Trial 1, NCT01907087).

Sixty-three percent of patients were female and 37% were male. Ninety-six percent of patients were White and 4% were Asian; for ethnicity, 4% identified as Hispanic/Latino, 96% as non-Hispanic/Latino. One patient withdrew after week 1 due to inability to continue with study procedures; 23 patients were treated with BRINEURA 300 mg every other week by intraventricular infusion for 48 weeks, and continued treatment during the 240-week extension period, Trial 2 (NCT02485899), for a total duration of 288 weeks, plus a 24-week safety follow-up.

In the clinical study with extension, patients were assessed for decline in the Motor domain of the CLN2 Clinical Rating Scale at 48, 72 and 96 weeks. Decline was defined as having an unreversed (sustained) 2-category decline or an unreversed score of 0 in the Motor domain of the CLN2 Clinical Rating Scale. Patients' responses to BRINEURA treatment were evaluated if at screening a combined Motor plus Language CLN2 score of less than 6 was recorded.

Two patients with a combined Motor plus Language CLN2 score of 6 were excluded from the analyses; they maintained that score throughout the study period. The patient who terminated early was analyzed as having a decline at the time of termination. Data used in the analyses from the natural history cohort began at 36 months of age or greater and at the first time a Motor plus Language CLN2 score less than 6 was recorded.

Motor scores of the 22 BRINEURA-treated patients in the clinical study with extension were compared to scores of the independent natural history cohort that included 42 untreated patients who satisfied inclusion criteria for the clinical study. The results of logistic modeling with covariates (screening age, screening motor score, genotype: 0 key mutations (yes/no)), demonstrated the odds of BRINEURA-treated patients not having a decline by 96 weeks were 13 times the odds of natural history cohort patients not having a decline (Odds Ratio (95% CI): 13.1 (1.2, 146.9)).

Descriptive non-randomized comparison In an unadjusted non-randomized comparison, of the 22 patients treated with BRINEURA and evaluated for efficacy at week 96, 21 (95%) did not decline, and only the patient who terminated early was deemed to have a decline in the Motor domain of the CLN2 Clinical Rating Scale. Results from the natural history cohort demonstrated progressive decline in motor function; of the 42 patients in the natural history cohort, 21 (50%) experienced an unreversed (sustained) 2-category decline or unreversed score of 0 in the Motor domain of the CLN2 Clinical Rating Scale over 96 weeks.

Given the non-randomized study design, a Cox Proportional Hazards Model adjusted for age, initial motor score, and genotype was used to evaluate time to unreversed 2-category decline or unreversed score of 0 in the Motor domain. This model showed a lesser decrease in motor function in the BRINEURA-treated patients when compared to the natural history cohort (see Figure 7 ). Figure 7.

Estimated… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 35 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, genotoxicity, and fertility studies have not been performed with cerliponase alfa. Based on the mechanism of action, cerliponase alfa is not expected to be tumorigenic.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 32 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, genotoxicity, and fertility studies have not been performed with cerliponase alfa. Based on the mechanism of action, cerliponase alfa is not expected to be tumorigenic.

📄 Recent Major Changes 32 words ▾

Boxed Warning 7/2024 Indication and Usage ( 1 ) 7/2024 Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.6 ) 7/2024 Warnings and Precautions ( 5.1 , 5.5 ) 7/2024

📄 Package Label / Principal Display Panel ~2 min read ▾

PRINCIPAL DISPLAY PANEL - Kit Carton - Package 1 NDC 68135-811-02 Brineura ® (cerliponase alfa) Injection 150 mg/5 mL (30 mg/mL) For Intraventricular Infusion Only Each vial of Brineura ® contains 150 mg cerliponase alfa in 5 mL of solution (30 mg/mL) No preservatives Single-Dose Vial. Discard unused portion. Brineura ® and Intraventricular Electrolytes must be administered with the Administration Kit provided.

Each carton contains: 2 vials, each containing Brineura ® (cerliponase alfa) Injection, 150 mg/5 mL 1 vial of Intraventricular Electrolytes Injection, 5 mL Package 1 of 2 Administration Kit is supplied and stored separately as package 2 of 2. Rx Only BIOMARIN ® PRINCIPAL DISPLAY PANEL - Kit Carton - Package 1

PRINCIPAL DISPLAY PANEL - 150 mg/5 mL Vial Label Brineura ® (cerliponase alfa) Injection 150 mg/5 mL (30 mg/mL) For Intraventricular Infusion Only Use before Intraventricular Electrolytes PRINCIPAL DISPLAY PANEL - 150 mg/5 mL Vial Label

PRINCIPAL DISPLAY PANEL - 5 mL Vial Label Intraventricular Electrolytes Injection Use after Brineura ® (cerliponase alfa) 5 mL For Intraventricular Infusion Only PRINCIPAL DISPLAY PANEL - 5 mL Vial Label

PRINCIPAL DISPLAY PANEL - Kit Carton - Package 2 Administration Kit for use with Brineura ® (cerliponase alfa) Intraventricular infusion only Recommended Dosage: See Prescribing Information Contents of Administration Kit: Two single-use 20-mL syringes Two single-use syringe needles, 21 G, 25.4 mm One single-use extension line One single-use infusion set with 0.2 micron inline filter One single-use port needle, 22 G, 16 mm Package 2 of 2 Brineura ® and Intraventricular Electrolytes Injection are separately supplied and stored frozen as package 1 of 2 Not for resale Only for use with Brineura ® Caution: - Do not use if the seals or package are damaged. - Do not resterilize. - Single use only.

Do not reuse. - Do not freeze. - Store in original package separately from Brineura ® . NOTE: - This Administration Kit has no components made of natural latex rubber. - Individual devices are provided in separate sterile packaging. - Expiration dates may vary for each device included. Manufactured for BioMarin Pharmaceutical Inc.

Novato, CA 94949 www.bmrn.com Rx Only BIOMARIN ® PRINCIPAL DISPLAY PANEL - Kit Carton - Package 2

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
72
Units reimbursed last 4 qtrs
144
Gross reimbursed last 4 qtrs
$1.93M
Avg / prescription
$26,783.59
Avg / unit
$13,391.79
Latest quarter Q1 2026
15Rx
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 72 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 144 units · 1.7 per 100k residents VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.71.7
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Virginia 1.7 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Brineura (this brand).

Top reported reactions

Pyrexia90
Seizure75
Vomiting37
Device Related Infection30
Device Leakage28
Csf Culture Positive26
Pneumonia25

Age at onset

Child40
Adolescent6
Adult2

Reporter sex

526 reports
Male · 55%
Female · 45%

Serious outcomes

Hospitalization193
Death24
Life-threatening18
Disabling5
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 83 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product Kit / multi-component package

Kit / multi-component package

This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.

What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by BioMarin Pharmaceutical Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
BioMarin Pharmaceutical Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
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For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.