Brineura Side Effects

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.

6.1 Clinical 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.