Galsulfase

FDA Drug Information • Also known as: Naglazyme

Brand Names: Naglazyme
Dosage Form: SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

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 NAGLAZYME 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 NAGLAZYME 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 NAGLAZYME 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 NAGLAZYME and immediately initiate appropriate medical treatment, including use of epinephrine. ( 5.1 )

Description

11 DESCRIPTION NAGLAZYME is a formulation of galsulfase, which is a purified human enzyme that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase (glycosaminoglycan N -acetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal enzyme that catalyzes the cleavage of the sulfate ester from terminal N –acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG), chondroitin 4-sulfate and dermatan sulfate. Galsulfase is a glycoprotein with a molecular weight of approximately 56 kDa. The recombinant protein consists of 495 amino acids and possesses six asparagine‑linked glycosylation sites, four of which carry a bis‑mannose-6–phosphate residue for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue, Cα-formylglycine, which is required for enzyme activity. NAGLAZYME has a specific activity of approximately 70 units per mg of protein content. One activity unit is defined as the amount of enzyme required to convert 1 micromole of 4-methylumbelliferyl sulfate to 4-methylumbelliferone and free sulfate per minute at 37°C. NAGLAZYME is intended for intravenous infusion and is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration. NAGLAZYME is supplied in clear Type I glass 5 mL vials. Each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80 in a 5 mL extractable solution with pH of approximately 5.8. NAGLAZYME does not contain preservatives. Each vial is for single use only.

What Is Galsulfase Used For?

1 INDICATIONS AND USAGE NAGLAZYME is indicated for patients with Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity. NAGLAZYME is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme indicated for patients with Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Administration of NAGLAZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. ( 2.1 ) The recommended dosage is 1 mg per kg of body weight administered once weekly as an intravenous infusion. ( 2.2 ) 2.1 Recommendations Prior to NAGLAZYME Treatment Administration of NAGLAZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1) ] . Initiate NAGLAZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1) ] . Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion [see Warnings and Precautions (5.5) ]. 2.2 Recommended Dosage and Administration The recommended dosage regimen of NAGLAZYME is 1 mg per kg of body weight administered once weekly as an intravenous infusion. The total volume of the infusion should be delivered over a period of time of no less than 4 hours. NAGLAZYME should be diluted with 0.9% Sodium Chloride Injection, USP, to a final volume of 250 mL and delivered by controlled intravenous infusion using an infusion pump. The initial infusion rate should be 6 mL per hour for the first hour. If the infusion is well tolerated, the rate of infusion may be increased to 80 mL per hour for the remaining 3 hours. The infusion time can be extended up to 20 hours if infusion reactions occur. For patients 20 kg and under or those who are susceptible to fluid volume overload, physicians may consider diluting NAGLAZYME in a volume of 100 mL [see Warnings and Precautions (5.3) ] . The infusion rate (mL per hour) should be decreased so that the total infusion duration remains no less than 4 hours. Each vial of NAGLAZYME provides 5 mg of galsulfase (expressed as protein content) in 5 mL of solution and is intended for single use only. Do not use the vial more than one time. The concentrated solution for infusion must be diluted with 0.9% Sodium Chloride Injection, USP, using aseptic techniques. Prepare NAGLAZYME using low-protein-binding containers and administer the diluted NAGLAZYME solution to patients using a low-protein-binding infusion set equipped with a low-protein-binding 0.2 µm in-line filter. There is no information on the compatibility of diluted NAGLAZYME with glass containers. 2.3 Instructions for Use Prepare and use NAGLAZYME according to the following steps. Use aseptic techniques. Determine the number of vials to be used based on the patient's weight and the recommended dose of 1 mg per kg: Patient's weight (kg) × 1 mL/kg of NAGLAZYME = Total number of mL of NAGLAZYME Total number of mL of NAGLAZYME ÷ 5 mL per vial = Total number of vials Round up to the next whole vial. Remove the required number of vials from the...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Serious and/or clinically significant adverse reactions described elsewhere in labeling include: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions ( 5.1 )] Immune-Mediated Reactions [see Warnings and Precautions ( 5.2 )] Risk of Acute Cardiorespiratory Failure [see Warnings and Precautions ( 5.2 )] Acute Respiratory Complications Associated with Administration [see Warnings and Precautions ( 5.4 )] Infusion Reactions [see Warnings and Precautions ( 5.5 )] Spinal or Cervical Cord Compression [see Warnings and Precautions ( 5.6 )] The most common adverse reactions (≥10%) are: rash, pain, urticaria, pyrexia, pruritus, chills, headache, nausea, vomiting, abdominal pain and dyspnea. The most common adverse reactions requiring interventions are infusion-related reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact: BioMarin Pharmaceutical Inc. 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 observed in the clinical trials of another drug and may not reflect the rates observed in clinical practice. NAGLAZYME was studied in a randomized, double-blind, placebo-controlled trial in which 19 patients received weekly infusions of 1 mg/kg NAGLAZYME and 20 patients received placebo; of the 39 patients 66% were female, and 62% were White, non-Hispanic. Patients were aged 5 years to 29 years. NAGLAZYME-treated patients were approximately 3 years older than placebo-treated patients (mean age 13.7 years versus 10.7 years, respectively). Serious adverse reactions experienced in this trial include apnea, pyrexia, and respiratory distress. Severe adverse reactions include chest pain, dyspnea, laryngeal edema, and conjunctivitis. The most common adverse reactions requiring interventions were infusion reactions . Table 1 summarizes the adverse reactions that occurred in the placebo-controlled trial in at least 2 patients more in the NAGLAZYME‑treated group than in the placebo-treated group. Table 1: Adverse Reactions that Occurred in the Placebo-Controlled Trial in at least 2 Patients More in the NAGLAZYME Group than in the Placebo Group NAGLAZYME (n = 19) Placebo (n = 20 One of the 20 patients in the placebo group dropped out after Week 4 infusion ) MedDRA Preferred Term No. Patients (%) No. Patients (%) All 19 (100) 20 (100) Abdominal Pain 9 (47) 7 (35) Ear Pain 8 (42) 4 (20) Arthralgia 8 (42) 5 (25) Pain 6 (32) 1 (5) Conjunctivitis 4 (21) 0 Dyspnea 4 (21) 2 (10) Rash 4 (21) 2 (10) Chills 4 (21) 0 Chest Pain 3 (16) 1 (5) Pharyngitis 2 (11) 0 Areflexia 2 (11) 0 Corneal Opacity 2 (11) 0 Gastroenteritis 2 (11) 0 Hypertension 2 (11) 0 Malaise 2 (11) 0 Nasal Congestion 2 (11) 0 Umbilical Hernia 2 (11) 0 Hearing Impairment 2 (11) 0 Four open-label clinical trials were conducted in MPS VI patients aged 3 months to 29 years with NAGLAZYME administered at doses of 0.2 mg/kg (n = 2), 1 mg/kg (n = 55), and 2 mg/kg (n = 2). The mean exposure to the recommended dose of NAGLAZYME (1 mg/kg) was 138 weeks (range = 54 to 261 weeks). Two infants (12.1 months and 12.7 months) were exposed to 2 mg/kg of NAGLAZYME for 105 and 81 weeks, respectively. In addition to those listed in Table 1, common adverse reactions observed in the open-label trials include pruritus, urticaria, pyrexia, headache, nausea, and vomiting. The most common adverse reactions requiring interventions were infusion reactions. Serious adverse reactions included laryngeal edema, urticaria, angioedema, and other hypersensitivity reactions. Severe adverse reactions included urticaria, rash, and abdominal pain. Observed adverse events in four open-label studies (up to 261 weeks treatment) were not different in nature or severity to those observed in the placebo-controlled study. No patients discontinued during open-label...

Contraindications

4 CONTRAINDICATIONS None. None. (4)

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Available data from a pregnancy sub-study within the MPS VI Clinical Surveillance Program and case reports with NAGLAZYME use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, galsulfase administered intravenously to pregnant rats and rabbits during the period of organogenesis, showed no evidence of harm to the fetus at doses of about 0.5 and 0.97 times, respectively for rats and rabbits, the recommended human dose of 1 mg/kg based on body surface area (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, 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. Clinical Considerations Disease-associated maternal and embryo/fetal risk Pregnancy can exacerbate preexisting clinical manifestations of MPS and lead to adverse pregnancy outcomes for both mother and fetus. Data Human Data Available data from a pregnancy sub-study within the MPS VI Clinical Surveillance Program and case reports with the use of NAGLAZYME during pregnancy have identified seventeen pregnancies. No major birth defects have been reported. Drug-associated adverse maternal and fetal outcomes have not been identified. Animal Data Reproduction studies have been performed with intravenous galsulfase during the period of organogenesis in pregnant rats at doses of galsulfase up to 3 mg/kg/day (about 0.5 times the recommended human dose of 1 mg/kg based on the body surface area) and in pregnant rabbits at doses up to 3 mg/kg/day (about 0.97 times the recommended human dose of 1 mg/kg based on the body surface area) and have revealed no evidence of harm to the fetus due to galsulfase.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING NAGLAZYME injection is supplied as a sterile colorless to pale yellow, clear to slightly opalescent solution in clear Type I glass 5 mL vials, containing 5 mg galsulfase (expressed as protein content) per 5 mL solution. The closure consists of a siliconized chlorobutyl rubber stopper and an aluminum seal with a plastic flip-off cap. NDC 68135-020-01, 5 mL vial Store NAGLAZYME under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. This product contains no preservatives.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.