Enzymes

Naglazyme

Approved 31 May 2005InjectionInjectable

Indications

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 )

Contraindications

None. None. (4)

Warnings and precautions

Immune-Mediated Reactions : Immune-mediated reactions can occur with NAGLAZYME. Monitor patients for the development of immune complex-mediated reactions while receiving NAGLAZYME. ( 5.2 ) Risk of Acute Cardiorespiratory Failure : Caution should be exercised when administering NAGLAZYME to patients susceptible to fluid volume overload. Consider a decreased total infusion volume and infusion rate when administering NAGLAZYME to these patients.

Appropriate medical monitoring and support measures should be available during infusion. ( 2.2 , 5.3 ) Acute Respiratory Complications : Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apneic episodes. Appropriate respiratory support should be available during infusion. ( 5.4 ) Infusion Reactions : Pretreatment with antihistamines with or without antipyretics is recommended prior to the start of infusion to reduce the risk of infusion-reactions.

If infusion reactions occur, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antihistamines and/or antipyretics is recommended. ( 2.2 , 5.5 )

5.1Hypersensitivity Reactions Including Anaphylaxis

Life-threatening hypersensitivity reactions, including anaphylaxis, have been observed in patients treated with enzyme replacement therapies, including NAGLAZYME. These reactions have occurred during and up to 24 hours after completion of the NAGLAZYME infusion. Some of the reactions included shock, respiratory distress, dyspnea, bronchospasm, laryngeal edema, and hypotension [see Adverse Reactions (6.1 , 6.2 )] . Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Administration of NAGLAZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. 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.

At a glance

Brand name: Naglazyme
Active substance: galsulfase
Drug class: Enzymes
Route: Injection
Dosage form: Injectable
Applicant: Biomarin
Status: Prescription
FDA approval: 31 May 2005
Application: BLA125117-001
RxCUI: 584219

Indications

Warnings and precautions

If infusion reactions occur, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antihistamines and/or antipyretics is recommended. ( 2.2 , 5.5 )

5.1Hypersensitivity Reactions Including Anaphylaxis

Pregnancy and breastfeeding

8.1Pregnancy 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.

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.

6.1Clinical 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 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 treatment with NAGLAZYME due to adverse events.

6.2Postmarketing Experience

The following adverse reactions have been identified during post approval use of NAGLAZYME. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serious infusion reactions : anaphylaxis, shock, hypotension, bronchospasm, and respiratory failure [see Warnings and Precautions ( 5.1 )] .

Additional infusion reactions : pyrexia, erythema, pallor, bradycardia, tachycardia, hypoxia, cyanosis, tachypnea, and paresthesia. During postmarketing surveillance, there has been a single case of membranous nephropathy and rare cases of thrombocytopenia reported. In the case of membranous nephropathy, renal biopsy revealed galsulfase‑immunoglobulin complexes in the glomeruli. With both membranous nephropathy and thrombocytopenia, patients have been successfully rechallenged and have continued to receive NAGLAZYME.

Naglazyme

Indications

Contraindications

Warnings and precautions

5.1Hypersensitivity Reactions Including Anaphylaxis

At a glance

Two medicines in one question?

Naglazyme

Indications

Contraindications

Warnings and precautions

5.1Hypersensitivity Reactions Including Anaphylaxis

At a glance

Two medicines in one question?

5.2Immune-Mediated Reactions Type

5.3Risk of Acute Cardiorespiratory Failure

5.4Acute Respiratory Complications Associated with Administration

5.6Spinal or Cervical Cord Compression Spinal

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information