Naglazyme

What Is Naglazyme and What Is It Used For?

Naglazyme (galsulfase) is an enzyme replacement therapy used to treat mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome), a rare inherited metabolic disorder. It provides the recombinant form of the enzyme N-acetylgalactosamine 4-sulfatase that is deficient or absent in patients with MPS VI.

Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme N-acetylgalactosamine 4-sulfatase (also known as arylsulfatase B). This enzyme is essential for the degradation of specific glycosaminoglycans (GAGs), particularly dermatan sulfate and chondroitin 4-sulfate. Without sufficient enzyme activity, these complex sugar molecules accumulate progressively in lysosomes throughout the body, leading to cellular dysfunction and multi-organ damage.

The accumulation of GAGs in MPS VI results in a wide range of clinical manifestations that typically become apparent in early childhood and worsen over time. Patients may experience skeletal abnormalities including short stature, joint stiffness, and dysostosis multiplex (a characteristic pattern of bone changes seen on X-rays). Cardiac complications such as valve disease and cardiomyopathy are common and represent a major cause of morbidity. Other features include corneal clouding, hearing loss, hepatosplenomegaly (enlarged liver and spleen), hernias, and upper airway obstruction. In severe cases, spinal cord compression may occur due to thickening of the dura mater or vertebral abnormalities.

Naglazyme contains galsulfase, a recombinant (genetically engineered) form of human N-acetylgalactosamine 4-sulfatase. It is produced using Chinese hamster ovary (CHO) cell technology, which allows the enzyme to be manufactured with the correct molecular structure and post-translational modifications needed for cellular uptake and lysosomal targeting. When administered intravenously, galsulfase is taken up by cells throughout the body via mannose-6-phosphate receptors on cell surfaces. Once internalised, the enzyme is transported to lysosomes where it catalyses the hydrolysis of the 4-sulfate ester groups from GAGs, thereby reducing their accumulation.

In the pivotal Phase III clinical trial (a randomised, double-blind, placebo-controlled study involving 39 patients), treatment with Naglazyme resulted in statistically significant improvements in the 12-minute walk test and the 3-minute stair climb compared to placebo. Patients receiving galsulfase also demonstrated significant reductions in urinary GAG levels, a key biomarker of disease severity. Long-term extension studies have shown that these benefits are sustained with continued weekly treatment over several years.

What Should You Know Before Receiving Naglazyme?

Before starting Naglazyme, inform your doctor about any previous allergic reactions to galsulfase, any existing heart or lung conditions, and whether you are pregnant or breastfeeding. Naglazyme is contraindicated in patients who have experienced severe or life-threatening hypersensitivity reactions to galsulfase that could not be managed upon re-administration.

Contraindications

You should not receive Naglazyme if any of the following apply to you:

• Severe or life-threatening allergic reactions (hypersensitivity) to galsulfase or any of the other ingredients in Naglazyme, where re-administration was not successful – symptoms of severe reactions include anaphylaxis, severe difficulty breathing, or cardiovascular collapse
• Known hypersensitivity to any excipient in the formulation, including sodium chloride, sodium phosphate, or polysorbate 80

It is important to note that unlike many other medicines, the contraindications for Naglazyme are relatively few, reflecting the severity of the underlying disease and the lack of alternative treatments. The decision to initiate or continue treatment is made on a case-by-case basis, weighing the potential benefits against the risks of infusion-related reactions.

Warnings and Precautions

Talk to your doctor before receiving Naglazyme if you have or have had any of the following conditions:

• Previous infusion-related reactions: If you have experienced reactions during previous infusions, your doctor may slow down the infusion rate or stop the infusion temporarily. Pre-medication with antihistamines, antipyretics (fever-reducing medicines), or corticosteroids may be given to help prevent reactions
• Fever or acute respiratory illness: If you have a fever or any difficulty breathing before your scheduled infusion, tell your doctor. The infusion may need to be delayed, as patients with an acute febrile or respiratory illness at the time of infusion may be at greater risk of life-threatening complications from infusion-related reactions
• Underlying heart disease: If you have any form of heart disease, inform your doctor at any point during treatment. Patients with MPS VI frequently develop cardiac complications, and your doctor may need to adjust the infusion parameters based on your cardiovascular status
• Kidney or liver problems: Naglazyme has not been tested in patients with significant renal or hepatic impairment. If you have reduced kidney or liver function, your doctor will monitor you closely during treatment
• Spinal cord compression: If you experience muscle pain, numbness in your arms or legs, or develop problems with bowel or bladder function, tell your doctor immediately. These symptoms may indicate spinal cord compression, which is a known complication of MPS VI and may require urgent medical intervention independent of Naglazyme treatment

Pregnancy and Breastfeeding

Naglazyme should not be used during pregnancy unless clearly necessary. There are insufficient data on the use of galsulfase in pregnant women, and it is not known whether galsulfase can cause harm to an unborn child. Animal reproduction studies have not been conducted with Naglazyme. If you are pregnant, think you might be pregnant, or are planning to become pregnant, you should discuss the risks and benefits of continuing treatment with your doctor.

It is not known whether galsulfase passes into breast milk. As a precaution, breastfeeding is not recommended during treatment with Naglazyme. If you are breastfeeding, talk to your doctor before your next infusion so that you can make an informed decision about whether to continue breastfeeding or continue treatment.

Driving and Operating Machinery

No formal studies have been conducted on the effects of Naglazyme on the ability to drive or operate machinery. However, some side effects of the infusion, such as dizziness or fatigue, may temporarily affect your ability to drive or use machines safely. If you experience any such symptoms during or after your infusion, you should avoid driving or operating machinery until you feel well enough to do so safely.

Sodium Content

Each 5 ml vial of Naglazyme contains 0.8 mmol (18.4 mg) of sodium. The medicine is also diluted in sodium chloride 9 mg/ml (0.9%) solution for infusion. This should be taken into consideration by patients on a controlled sodium diet, particularly those with heart failure, kidney disease, or hypertension. Your doctor will consider the total sodium load when calculating your infusion parameters.

How Does Naglazyme Interact with Other Drugs?

No formal drug interaction studies have been conducted with Naglazyme. However, Naglazyme should not be mixed with other medications in the same infusion line (except 0.9% sodium chloride solution). Always inform your doctor about all medicines you are taking, including over-the-counter products and supplements.

Because galsulfase is a recombinant human enzyme rather than a small-molecule drug, it is not expected to undergo the same cytochrome P450 (CYP)-mediated metabolic interactions that are common with conventional pharmaceuticals. The enzyme is degraded through normal protein catabolism pathways. Consequently, formal drug-drug interaction studies have not been performed with Naglazyme, and there are no known clinically significant pharmacokinetic interactions with other medicines.

However, there are several important practical considerations regarding concomitant medications in patients receiving Naglazyme:

Infusion Compatibility

Naglazyme must not be mixed with other medicinal products in the same infusion bag or infusion line, with the exception of 0.9% sodium chloride solution used for dilution. Mixing with other drugs could alter the stability, efficacy, or safety profile of galsulfase. If other intravenous medications are needed, they should be administered through a separate line or at a different time.

Pre-Medications for Infusion Reactions

Many patients receiving Naglazyme are pre-medicated with antihistamines (such as diphenhydramine or cetirizine) and/or antipyretics (such as paracetamol/acetaminophen) approximately 30 to 60 minutes before the infusion begins. In patients who have experienced more severe infusion-related reactions, corticosteroids (such as methylprednisolone or hydrocortisone) may also be given prior to infusion. These pre-medications are generally well tolerated and do not interact with galsulfase itself.

Other Medication Considerations

Patients with MPS VI often take multiple medications to manage the various complications of the disease, including cardiac medications, analgesics, and respiratory therapies. There is no evidence that galsulfase interacts adversely with any of these treatments. However, it is always important to inform your healthcare team about all medicines you are taking, including:

• Prescription medications for heart problems, pain, or breathing difficulties
• Over-the-counter medicines, vitamins, and dietary supplements
• Herbal remedies or alternative medicines

If you are receiving other enzyme replacement therapies or biological medicines for different conditions, your doctor will need to carefully coordinate the timing and administration of these treatments to avoid potential complications.

What Is the Correct Dosage of Naglazyme?

The recommended dose of Naglazyme is 1 mg per kilogram of body weight, given once weekly as an intravenous infusion over approximately 4 hours. The infusion must be administered under the supervision of a physician or nurse experienced in the management of MPS VI or other metabolic diseases.

Naglazyme is administered as a slow intravenous infusion through a drip in a vein. The dose is weight-based and remains the same for all age groups and patient populations. Each infusion session lasts approximately 4 hours and follows a specific rate protocol designed to minimise the risk of infusion-related reactions.

Adults

The gradual ramp-up of the infusion rate during the first hour is a critical safety measure. Starting slowly allows the healthcare team to monitor for early signs of infusion-related reactions before the bulk of the medication is administered. If the patient tolerates the initial rate well, the infusion rate is increased for the remainder of the infusion. Your doctor may adjust the infusion rate based on your individual tolerance and clinical response.

Children

MPS VI is typically diagnosed in childhood, and treatment with Naglazyme often begins in the paediatric age group. The weight-based dosing ensures that children receive an appropriate amount of enzyme relative to their body size. Clinical studies have included patients as young as 5 years of age, and the safety and efficacy profile in children is generally consistent with that observed in adults.

Elderly Patients

There is limited clinical experience with Naglazyme in patients over 65 years of age. MPS VI is a condition typically diagnosed in childhood, and many patients have a reduced life expectancy if untreated. Dose adjustment based on age alone is not expected to be necessary, but elderly patients may have concurrent medical conditions (particularly cardiovascular and respiratory) that require careful monitoring during infusion. The dose remains 1 mg/kg body weight given weekly.

Missed Dose

If you miss a scheduled Naglazyme infusion, contact your doctor or treatment centre as soon as possible to arrange a replacement appointment. Because Naglazyme is administered by healthcare professionals in a clinical setting, missed doses are typically rescheduled promptly. It is important to maintain the regular weekly infusion schedule to achieve optimal therapeutic benefit. Do not attempt to receive a double dose to compensate for a missed infusion.

Overdose

Naglazyme is administered under the direct supervision of a physician or nurse, who will carefully calculate and verify the dose based on your body weight. No cases of overdose have been reported in clinical trials or post-marketing experience. If an overdose were to occur, the infusion would be stopped immediately, and the patient would be monitored for any adverse reactions. Treatment would be supportive and symptomatic, with particular attention to respiratory function and cardiovascular status.

What Are the Side Effects of Naglazyme?

Like all medicines, Naglazyme can cause side effects, although not everybody gets them. The most common side effects are infusion-related reactions, which occur during or shortly after the infusion. These include fever, chills, rash, urticaria (hives), and breathing difficulties. Most side effects can be managed by slowing or temporarily stopping the infusion and administering appropriate treatment.

Side effects with Naglazyme are most commonly seen during the infusion itself or within the remainder of the day on which the infusion is given (known as “infusion-related reactions”). The most serious potential side effects include facial and tongue swelling, throat swelling, severe allergic reactions (anaphylaxis), and respiratory distress. If you experience any of these severe symptoms, your healthcare team will take immediate action, which may include stopping the infusion and administering emergency medication such as adrenaline (epinephrine), antihistamines, and corticosteroids.

The development of anti-galsulfase antibodies (IgG) has been observed in the majority of patients treated with Naglazyme. While the presence of antibodies does not necessarily reduce the clinical efficacy of the treatment, it may be associated with an increased frequency or severity of infusion-related reactions. Your doctor may periodically test for antibody levels as part of ongoing treatment monitoring.

Managing Infusion-Related Reactions

If you experience an infusion-related reaction, your healthcare team has several strategies available to manage it safely:

• Slowing the infusion rate: Reducing the speed at which the medicine is delivered often resolves mild symptoms
• Temporarily stopping the infusion: For moderate reactions, the infusion may be paused until symptoms resolve, then restarted at a slower rate
• Administering additional medications: Antihistamines, corticosteroids, or antipyretics may be given to manage allergic symptoms, inflammation, or fever
• Stopping the infusion completely: In cases of severe or life-threatening reactions (such as anaphylaxis), the infusion will be stopped immediately and emergency treatment will be provided

Over time, many patients find that infusion-related reactions become less frequent and less severe as they continue treatment. Your doctor will develop an individualised management plan based on your reaction history and will adjust pre-medication and infusion rates accordingly.

Reporting Side Effects

It is important to report any suspected side effects to your healthcare provider. Reporting side effects after a medicine has been authorised helps to continuously monitor the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report suspected adverse reactions through their national adverse drug reaction reporting system.

How Should You Store Naglazyme?

Unopened Naglazyme vials must be stored in a refrigerator at 2–8°C and must not be frozen. The diluted solution should be used immediately, but if necessary can be stored for up to 24 hours at 2–8°C followed by up to 24 hours at room temperature during infusion.

As Naglazyme is administered in a clinical setting by healthcare professionals, you will not typically need to store the medication yourself. However, understanding the storage requirements is important for ensuring the quality and safety of the product you receive.

Storage Conditions

• Unopened vials: Store in a refrigerator at 2°C to 8°C. Keep the vials in the outer carton to protect from light
• Do not freeze: Freezing can damage the protein structure of galsulfase, rendering the product ineffective
• Do not use after the expiry date: Check the date printed on the vial label (EXP). The expiry date refers to the last day of the stated month
• Visual inspection: Before use, the solution should be inspected for visible particles or discolouration. The concentrate should be clear to slightly opalescent, and colourless to pale yellow. Do not use if particles are visible or if the solution appears discoloured

Diluted Solution Storage

Once diluted for infusion, the Naglazyme solution has been shown to be chemically and physically stable for up to 4 days at room temperature (23–27°C). However, from a microbiological standpoint, it should be used immediately. If not used immediately, in-use storage times should not normally exceed 24 hours at 2–8°C followed by a maximum of 24 hours at room temperature (23–27°C) during the infusion period.

Disposal

Each vial of Naglazyme is intended for single use only. Any unused product or waste material should be disposed of in accordance with local requirements for pharmaceutical waste. Do not dispose of medicines via household waste or wastewater. These measures help to protect the environment.

What Does Naglazyme Contain?

Naglazyme contains the active substance galsulfase (1 mg/ml). Each 5 ml vial contains 5 mg of galsulfase, which is the recombinant human form of the enzyme N-acetylgalactosamine 4-sulfatase, produced using genetically modified Chinese hamster ovary (CHO) cells.

Active Ingredient

The active substance in Naglazyme is galsulfase. Each millilitre of concentrate contains 1 mg of galsulfase, and each 5 ml vial contains 5 mg of galsulfase in total. Galsulfase is the recombinant (genetically engineered) form of the naturally occurring human enzyme N-acetylgalactosamine 4-sulfatase (arylsulfatase B). It is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cell lines, which have been genetically modified to express the human enzyme. The manufacturing process includes extensive purification steps to ensure a high-purity product suitable for intravenous administration.

Other Ingredients (Excipients)

In addition to the active substance, Naglazyme contains the following inactive ingredients:

• Sodium chloride – provides isotonicity and helps stabilise the protein
• Sodium dihydrogen phosphate monohydrate – buffer component to maintain pH stability
• Disodium hydrogen phosphate heptahydrate – buffer component to maintain pH stability
• Polysorbate 80 – surfactant that helps prevent protein aggregation and adsorption to surfaces
• Water for injections – solvent

Appearance and Pack Sizes

Naglazyme is supplied as a concentrate for solution for infusion. The concentrate is a clear to slightly opalescent, colourless to pale yellow liquid that must be free of visible particles. Before administration, it must be diluted with 0.9% sodium chloride solution for infusion. Naglazyme is available in packs containing 1 or 6 vials. Not all pack sizes may be marketed in every country.

How Does Naglazyme Work?

Naglazyme works by providing a functional replacement for the deficient enzyme N-acetylgalactosamine 4-sulfatase in patients with MPS VI. The exogenous enzyme is taken up by cells via mannose-6-phosphate receptors, delivered to lysosomes, and catalyses the breakdown of accumulated glycosaminoglycans (GAGs).

The mechanism of action of Naglazyme is based on the principle of enzyme replacement therapy (ERT). In healthy individuals, the enzyme N-acetylgalactosamine 4-sulfatase (arylsulfatase B) is produced naturally within cells and is targeted to lysosomes, where it plays a critical role in the stepwise degradation of dermatan sulfate and chondroitin 4-sulfate, two types of glycosaminoglycans (GAGs). These GAGs are complex sugar molecules that form an essential part of connective tissues, including cartilage, tendons, corneas, skin, and blood vessel walls.

In patients with MPS VI, mutations in the ARSB gene result in absent or markedly reduced activity of N-acetylgalactosamine 4-sulfatase. Without this enzyme, GAGs cannot be properly degraded within lysosomes. As a result, partially digested GAG fragments accumulate progressively within the lysosomes of cells throughout the body. This lysosomal engorgement leads to cellular dysfunction, tissue damage, and organ failure over time.

When galsulfase is administered intravenously, it circulates in the bloodstream and is recognised by mannose-6-phosphate (M6P) receptors on cell surfaces. These receptors bind to the mannose-6-phosphate residues on the enzyme and facilitate its internalisation into the cell through receptor-mediated endocytosis. Once inside the cell, galsulfase is transported to lysosomes, where it functions as a replacement for the deficient native enzyme. Within the lysosome, galsulfase catalyses the hydrolysis of the 4-sulfate ester groups from dermatan sulfate and chondroitin 4-sulfate, enabling their further degradation by other lysosomal enzymes.

The pharmacokinetic profile of galsulfase changes with continued treatment. After the first infusion, the elimination half-life is approximately 9 minutes, reflecting rapid clearance primarily through M6P receptor-mediated uptake into tissues. After several weeks of weekly infusions, the half-life increases to approximately 26 minutes at steady state. This change is thought to reflect a degree of saturation of the M6P receptors and a reduction in the overall GAG burden in tissues.

Clinical evidence demonstrates that regular treatment with Naglazyme leads to measurable reductions in urinary GAG levels (a biomarker of disease burden), as well as clinically meaningful improvements in endurance and physical function. These effects are consistent with the successful replacement of the missing enzyme and the consequent reduction in lysosomal GAG storage. However, enzyme replacement therapy does not cross the blood-brain barrier in significant quantities, and Naglazyme is therefore not expected to address any neurological manifestations that may be present in some MPS VI patients.

Frequently Asked Questions