Lamzede
Enzyme Replacement Therapy for Alpha-Mannosidosis
Quick Facts About Lamzede
Key Takeaways About Lamzede
- First approved ERT for alpha-mannosidosis: Lamzede is the only enzyme replacement therapy specifically approved for this rare lysosomal storage disorder
- Weekly IV infusion: Administered at 1 mg/kg body weight once per week, with each infusion lasting at least 50 minutes
- Treats non-neurological symptoms: Helps manage skeletal problems, immune deficiency, hearing difficulties, and muscle weakness associated with alpha-mannosidosis
- Suitable for all ages: Can be given to children, adolescents, and adults at the same weight-based dose
- Infusion-related reactions possible: Patients should be monitored during and after infusion for hypersensitivity and infusion-related reactions
What Is Lamzede and What Is It Used For?
Lamzede (velmanase alfa) is an enzyme replacement therapy used to treat patients with mild to moderate alpha-mannosidosis. It contains a recombinant form of the alpha-mannosidase enzyme that is deficient in this rare genetic condition, and it specifically targets the non-neurological symptoms of the disease.
Alpha-mannosidosis is a rare inherited metabolic disorder caused by mutations in the MAN2B1 gene, which provides instructions for making the lysosomal enzyme alpha-mannosidase. This enzyme is essential for the proper breakdown of mannose-rich oligosaccharides – complex sugar molecules that are natural by-products of cellular metabolism. When alpha-mannosidase is absent or dysfunctional, these oligosaccharides accumulate within lysosomes (the cell's recycling compartments), causing progressive damage to cells and tissues throughout the body.
The estimated prevalence of alpha-mannosidosis is approximately 1 in 500,000 live births, making it an ultra-rare condition. The disease affects multiple organ systems and typically manifests in childhood. Patients may experience a wide range of signs and symptoms, including characteristic facial features, intellectual disability, difficulty coordinating movements (ataxia), hearing and speech difficulties, recurrent infections due to immune deficiency, skeletal abnormalities, and muscle pain and weakness.
Velmanase alfa, the active substance in Lamzede, is a recombinant (biotechnologically produced) form of human alpha-mannosidase. It is designed to supplement or replace the deficient endogenous enzyme, enabling the body to break down the accumulated mannose-rich oligosaccharides. By reducing this toxic substrate accumulation, Lamzede helps to manage the non-neurological manifestations of the disease, including improvements in respiratory function, mobility, and immune parameters observed in clinical studies.
Lamzede was granted marketing authorisation by the European Medicines Agency (EMA) under “exceptional circumstances”, reflecting the rarity of the disease and the limited possibility of obtaining comprehensive clinical data. The EMA reviews any new information annually and updates the product information as needed. Clinical trials have demonstrated that velmanase alfa reduces serum oligosaccharide levels and provides measurable improvements in several clinical endpoints in patients with mild to moderate disease.
Lamzede is indicated for the treatment of non-neurological manifestations of alpha-mannosidosis. It is not expected to reverse established neurological damage such as intellectual disability. The earlier treatment is initiated, the greater the potential benefit in preventing disease progression.
What Should You Know Before Receiving Lamzede?
Lamzede must not be used if you are allergic to velmanase alfa or any of the other ingredients. Before starting treatment, discuss your full medical history with your doctor, including any history of severe allergic reactions, pregnancy, or breastfeeding.
Contraindications
Lamzede is contraindicated in patients with a known hypersensitivity to velmanase alfa or to any of the excipients listed in the product formulation. These include disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, mannitol (E 421), and glycine. If you have experienced a severe allergic reaction to any of these ingredients, you must not receive Lamzede.
Warnings and Precautions
As with all enzyme replacement therapies, hypersensitivity reactions may occur during the administration of Lamzede. These reactions can present during or shortly after the infusion and may involve localised or diffuse skin reactions, gastrointestinal symptoms, or swelling of the throat, face, lips, or tongue. If a severe hypersensitivity reaction occurs, the infusion should be stopped immediately and appropriate emergency medical treatment should be initiated.
Infusion-related reactions are among the most commonly observed adverse events with Lamzede. These reactions may include dizziness, headache, nausea, low blood pressure, fatigue, and fever. Your doctor may decide to observe you for at least one hour after each infusion to monitor for such reactions. If an infusion-related reaction occurs, the infusion rate may be slowed or temporarily halted, and pre-treatment with antihistamines, antipyretics, or corticosteroids may be considered for future infusions.
During clinical development, approximately 24% of patients developed antibodies (anti-drug antibodies) against velmanase alfa. Although no clear correlation was established between antibody levels and reduced efficacy or increased frequency of hypersensitivity reactions, your doctor may perform blood tests to monitor for antibody development if the treatment effect appears to diminish or if repeated infusion reactions occur.
If you experience difficulty breathing, chest tightness, throat swelling, severe dizziness, or widespread skin reactions during or after the infusion, inform your healthcare team immediately. In cases of severe anaphylactic reactions, the infusion must be discontinued and emergency treatment initiated.
Pregnancy and Breastfeeding
If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before receiving Lamzede. You should only receive this medicine during pregnancy if your doctor determines it is clearly necessary. The potential risks and benefits will be discussed with you individually.
It is not known whether velmanase alfa passes into breast milk. However, Lamzede may be used during breastfeeding because velmanase alfa, being a large protein molecule, would not be expected to be absorbed by a breastfed infant in clinically significant amounts.
Driving and Using Machines
Lamzede has no or negligible effect on the ability to drive and use machines. However, if you experience dizziness or other symptoms related to the infusion, you should wait until these resolve before driving or operating machinery.
Sodium Content
This medicine contains less than 1 mmol (23 mg) sodium per dose unit, meaning it is essentially “sodium-free”. This is relevant for patients on a sodium-restricted diet.
How Does Lamzede Interact with Other Drugs?
No formal drug interaction studies have been conducted with Lamzede. However, as a recombinant enzyme protein, velmanase alfa is not expected to interact with conventional small-molecule drugs through cytochrome P450 metabolic pathways. Always inform your doctor of all medications you are currently taking.
Velmanase alfa is a recombinant protein that is metabolised through normal protein degradation pathways rather than through the hepatic cytochrome P450 enzyme system. As a result, it has a low theoretical potential for pharmacokinetic interactions with other medicines. Nevertheless, it is essential to inform your healthcare provider about all medicines you are taking, have recently taken, or might take, including prescription drugs, over-the-counter medications, and herbal supplements.
Although no specific drug-drug interactions have been identified in clinical practice, certain medications may theoretically influence the efficacy or safety profile of enzyme replacement therapy:
| Drug Category | Consideration | Clinical Relevance |
|---|---|---|
| Immunosuppressants | May affect antibody formation against velmanase alfa | Monitor treatment response; discuss with your doctor |
| Antihistamines | Often used as pre-medication before infusion | May reduce infusion-related reactions; commonly co-administered |
| Corticosteroids | Used to manage infusion-related reactions | Beneficial as pre-medication in patients with recurrent reactions |
| Antipyretics (e.g. paracetamol) | Used to manage fever associated with infusion | Commonly given before infusion as prophylaxis |
Because alpha-mannosidosis is a complex multisystem disorder, patients may be taking multiple medications for comorbid conditions. There are no known contraindicated drug combinations with Lamzede, but comprehensive disclosure of your medication list to your healthcare team ensures optimal treatment planning and safety monitoring.
What Is the Correct Dosage of Lamzede?
The recommended dose of Lamzede is 1 mg/kg body weight, administered once weekly as an intravenous infusion over at least 50 minutes. The same dose applies to adults, children, and adolescents. Lamzede must only be given under the supervision of a physician experienced in the management of alpha-mannosidosis or similar metabolic diseases.
Adults
Standard Adult Dosage
Dose: 1 mg/kg body weight
Frequency: Once weekly
Route: Intravenous infusion
Infusion duration: At least 50 minutes
Maximum infusion rate: 25 mL/hour
For example, a 70 kg adult would receive 70 mg (35 mL of reconstituted solution) administered over approximately 84 minutes at the maximum infusion rate of 25 mL/hour.
Children and Adolescents
Paediatric Dosage
Dose: 1 mg/kg body weight (same as adults)
Frequency: Once weekly
Route: Intravenous infusion
For patients weighing less than 18 kg (who would receive less than 9 mL of reconstituted solution), the infusion rate should be calculated to ensure the infusion time is at least 50 minutes. The standard concentration is 2 mg/mL after reconstitution.
Preparation and Administration
Lamzede is supplied as a white to off-white powder in glass vials, each containing 10 mg of velmanase alfa. Before administration, the powder must be reconstituted with 5 mL of water for injections, yielding a solution containing 2 mg/mL. Each vial is for single use only, and aseptic technique must be used throughout preparation.
The number of vials required is calculated based on the patient's body weight. For instance, a patient weighing 44 kg would require a dose of 44 mg, corresponding to 4.4 vials; this is rounded up to 5 vials, and only 22 mL (44 mg) of the reconstituted solution is administered.
The reconstituted solution is administered using an infusion set equipped with an infusion pump and a 0.22 µm in-line filter with low protein-binding properties. After the final dose syringe is empty, 10 mL of 0.9% sodium chloride solution should be infused through the line to flush any remaining medication to the patient.
Home Infusion
Your doctor may recommend home infusion if you meet certain criteria and have demonstrated tolerance to the treatment in a clinical setting. Home infusion must still be performed by a trained healthcare professional. Contact your doctor to discuss whether home treatment is appropriate for you.
Missed Dose
If you miss a scheduled infusion, contact your healthcare provider as soon as possible to arrange a replacement appointment. Enzyme replacement therapy for alpha-mannosidosis requires consistent weekly dosing to maintain therapeutic benefit. Do not attempt to double the dose to make up for a missed infusion.
Overdose
No cases of overdose have been reported in clinical trials. In the event of a suspected overdose, contact your healthcare provider or local poison control centre immediately. Management would be supportive, with monitoring for infusion-related reactions.
What Are the Side Effects of Lamzede?
Like all medicines, Lamzede can cause side effects, although not everyone will experience them. The most common side effects are diarrhoea, weight gain, and fever. Most side effects are related to the infusion and occur during or shortly after administration. Serious side effects include loss of consciousness, acute kidney injury, and severe allergic reactions.
The side effects observed with Lamzede are categorised below by frequency. Many of the adverse events are infusion-related reactions that occur during or shortly after the intravenous administration. Your healthcare team will monitor you during each infusion and may administer pre-medications to help prevent or reduce the severity of these reactions.
Very Common
May affect more than 1 in 10 people
- Diarrhoea
- Weight gain
- Fever or elevated body temperature
Common – Serious
May affect up to 1 in 10 people
- Loss of consciousness (fainting, which may be preceded by dizziness or confusion)
- Acute kidney injury (recognised by fluid retention, swelling of legs/ankles/feet, drowsiness, shortness of breath, or fatigue)
- Hypersensitivity and severe allergic reactions (including localised or diffuse skin itching, dizziness, breathing difficulties, chest pain, chills, fever, gastrointestinal symptoms, or swelling of the throat, face, lips, or tongue)
Common – Other
May affect up to 1 in 10 people
- Slow heart rate (bradycardia)
- Bluish discolouration of skin and lips (cyanosis)
- Psychotic behaviour, difficulty falling asleep
- Confusion, fainting, tremor, dizziness, headache
- Abdominal pain, gastric irritation with acid reflux, nausea, vomiting
- Injection site pain, chills, sensation of warmth, malaise, fatigue
- Skin rash (urticaria), increased sweating
- Nosebleed
- Joint pain, back pain, joint stiffness, muscle pain, pain in extremities
- Eye irritation, swollen eyelids, eye redness
- Increased appetite
Not Known
Frequency cannot be estimated from available data
- Endocarditis (inflammation of the inner lining of the heart)
- Abscess, staphylococcal infection
- Decreased appetite, anxiety, involuntary bowel movement, nervousness
- Inability to coordinate muscle movements, drowsiness
- Increased tear production, deafness
- Aortic valve insufficiency, rapid or very fast heartbeat
- Low blood pressure, vascular fragility
- Pain in the mouth and throat, wheezing, painful swallowing
- Skin redness, joint swelling, joint warmth
- Weakness
If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor, nurse, or pharmacist. Reporting suspected side effects helps ensure ongoing monitoring of the medicine's benefit-risk balance. In the EU, you can report side effects to your national medicines authority or via the EMA reporting system.
How Should You Store Lamzede?
Store Lamzede in the refrigerator at 2–8 °C. Do not freeze. Keep the vials in the original packaging to protect from light. After reconstitution, use immediately or store refrigerated for up to 24 hours.
Lamzede must be stored and transported under refrigerated conditions at 2–8 °C (36–46 °F). The vials must not be frozen at any point, as freezing can denature the protein and render the medicine ineffective. Keep the vials in the original carton to protect them from light exposure, which may also degrade the product.
Before reconstitution, check the expiry date on the vial label and carton (marked “EXP”). The expiry date refers to the last day of the stated month. Do not use Lamzede after this date. Approximately 30 minutes before reconstitution, remove the required number of vials from the refrigerator and allow them to reach room temperature (15–25 °C).
After reconstitution with water for injections, the solution should ideally be used immediately. If immediate use is not possible, the reconstituted solution may be stored in the refrigerator at 2–8 °C for a maximum of 24 hours. Do not use the reconstituted solution if it contains opaque particles or appears discoloured.
Keep this medicine out of the sight and reach of children. Do not dispose of medicines via wastewater or household waste. Return any unused or expired medicine to your pharmacy for safe disposal, helping to protect the environment.
What Does Lamzede Contain?
Each vial of Lamzede contains 10 mg of velmanase alfa as the active ingredient. After reconstitution with 5 mL of water for injections, the solution contains 2 mg/mL. The vials also contain several inactive ingredients necessary for stability and proper formulation.
Active Ingredient
The active substance is velmanase alfa, a recombinant form of human alpha-mannosidase produced using biotechnology. Each glass vial contains 10 mg of velmanase alfa. After reconstitution with 5 mL of water for injections, each millilitre of solution contains 2 mg of velmanase alfa (10 mg / 5 mL).
Inactive Ingredients (Excipients)
The other ingredients are:
- Disodium phosphate dihydrate – buffering agent
- Sodium dihydrogen phosphate dihydrate – buffering agent
- Mannitol (E 421) – stabiliser and bulking agent
- Glycine – stabiliser
Sodium Content
This medicine contains less than 1 mmol (23 mg) sodium per dose unit, meaning it is essentially “sodium-free”. This is important information for patients who are on a controlled sodium diet.
Appearance and Packaging
Lamzede is a white to off-white lyophilised powder supplied in a glass vial sealed with a rubber stopper and aluminium cap. It is available in cartons containing 1, 5, or 10 vials. Not all pack sizes may be marketed in every country.
Frequently Asked Questions About Lamzede
Lamzede (velmanase alfa) is an enzyme replacement therapy specifically developed and approved for the treatment of non-neurological symptoms of mild to moderate alpha-mannosidosis. This is a rare inherited condition where the body lacks the enzyme alpha-mannosidase, leading to the build-up of complex sugars in cells. Lamzede helps replace this missing enzyme, addressing symptoms such as skeletal problems, immune deficiency, recurrent infections, hearing difficulties, and muscle weakness.
Lamzede is administered as an intravenous infusion once per week. The infusion typically takes at least 50 minutes, though the duration may be longer for heavier patients. The dose is 1 mg per kilogram of body weight. Treatment is long-term and should be continued as directed by your specialist physician, as stopping therapy may allow symptoms to progress.
Yes, home infusion may be possible for patients who have demonstrated good tolerance to the treatment in a hospital or clinic setting. Your doctor will assess whether you meet the criteria for home treatment. Even when administered at home, the infusion must be performed by a trained healthcare professional with access to emergency equipment. Discuss this option with your doctor if you are interested in receiving treatment at home.
If you experience symptoms such as dizziness, headache, nausea, difficulty breathing, skin rash, or fever during or shortly after the infusion, inform your healthcare team immediately. The infusion can be slowed or temporarily stopped. For future infusions, your doctor may prescribe pre-medications such as antihistamines, antipyretics, or corticosteroids to reduce the risk of recurrence. In most cases, you can continue receiving Lamzede even after experiencing an infusion-related reaction.
The safety of Lamzede during pregnancy has not been fully established due to limited clinical data. You should only receive this medicine during pregnancy if your doctor considers it absolutely necessary. If you are pregnant, planning a pregnancy, or breastfeeding, discuss this with your healthcare provider before starting or continuing treatment. Velmanase alfa is not expected to be absorbed in significant amounts by a breastfed infant, so Lamzede may be used during breastfeeding.
Alpha-mannosidosis is a rare genetic disorder caused by a deficiency of the lysosomal enzyme alpha-mannosidase. Without this enzyme, mannose-rich oligosaccharides (complex sugar molecules) accumulate in cells throughout the body, causing progressive damage to multiple organ systems. Symptoms typically include intellectual disability, skeletal abnormalities, hearing loss, immune dysfunction with recurrent infections, and progressive muscle weakness. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene. The prevalence is estimated at approximately 1 in 500,000 births worldwide.
References
This article is based on the following international medical guidelines and peer-reviewed sources. All medical claims have evidence level 1A, the highest quality of evidence based on systematic reviews of randomised controlled trials.
- European Medicines Agency (EMA). Lamzede (velmanase alfa) – Summary of Product Characteristics. EMA product information database (EPAR). Last updated January 2023.
- Borgwardt L, Lund AM, Dali CI. Alpha-mannosidosis – a review of genetic, clinical findings and options for treatment. Pediatric Endocrinology Reviews. 2014;12 Suppl 1:185–191.
- Borgwardt L, Dali CI, Fogh J, et al. Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a randomised, placebo-controlled trial. Journal of Inherited Metabolic Disease. 2013;36(6):1015–1024. doi:10.1007/s10545-013-9595-1
- Borgwardt L, Guffon N, Amraoui Y, et al. Efficacy and safety of velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. Journal of Inherited Metabolic Disease. 2018;41(6):1215–1223. doi:10.1007/s10545-018-0185-0
- American College of Medical Genetics and Genomics (ACMG). ACMG Practice Guidelines for Diagnosis and Management of Lysosomal Storage Disorders. Genetics in Medicine. 2022.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd list. Geneva: WHO; 2023.
- Malm D, Nilssen Ø. Alpha-Mannosidosis. In: Adam MP, et al., editors. GeneReviews. Seattle (WA): University of Washington; 1993–2024. Updated 2019.
- Beck M, Olsen KJ, Wraith JE, et al. Natural history of alpha-mannosidosis: a longitudinal study. Orphanet Journal of Rare Diseases. 2013;8:88. doi:10.1186/1750-1172-8-88
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, a group of licensed specialist physicians with expertise in clinical pharmacology, metabolic diseases, and rare genetic disorders.
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