Elosulfase alfa is a medication used in the treatment of mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome. MPS IVA is a rare genetic disorder caused by the deficiency of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS), which is responsible for breaking down certain complex sugars in the body.

Elosulfase alfa is a form of recombinant human N-acetylgalactosamine-6-sulfatase (GALNS) produced by genetic engineering. It works by replacing the missing or deficient GALNS enzyme, helping to break down the accumulated complex sugars in the body. This treatment aims to alleviate symptoms and improve the quality of life for individuals with MPS IVA.

A once-weekly injectable medication called elosulfase alfa (Vimizim) is recommended for the treatment of Morquio A syndrome.

The condition known as Morquio A syndrome, which is caused by an enzyme deficiency, is also known as mucopolysaccharidosis Type IV A.

Elosulfase alfa (Vimizim) Uses:

• Mucopolysaccharidosis type IVA:
  • It is used to treat patients with Treatment of Morquio A syndrome (mucopolysaccharidosis type IVA, MPS IVA)

Elosulfase alfa (Vimizim) Dose in Adults

Note: To avoid allergic reactions, doctors often give patients antihistamines before the treatment.

Elosulfase alfa (Vimizim) Dose in the treatment of Mucopolysaccharidosis type IVA (MPS IVA):

Elosulfase alfa is a medicine used to treat a rare genetic disorder called Morquio A syndrome. People with this condition lack a certain enzyme needed to break down complex sugars in their bodies. Elosulfase alfa helps by replacing this missing enzyme.

• The dose is usually injected into a vein once a week, with the amount depending on the person's weight (2 milligrams per kilogram).
• This treatment doesn't cure the condition but can help manage symptoms and improve quality of life.

Elosulfase alfa (Vimizim) Dose in Children

Note:

• Before giving elosulfase alfa to treat Morquio A syndrome, it's important to give the patient antihistamines (which can help prevent allergic reactions) with or without antipyretics (to reduce fever) about 30 to 60 minutes before the infusion.

Elosulfase alfa (Vimizim) Dose in the treatment of Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome):

• Children over 5 years and Adolescents:
  • The usual dose for elosulfase alfa in treating Morquio A syndrome is 2 milligrams per kilogram of body weight.
  • This is given once a week through an intravenous (IV) infusion.

Canadian labeling:

• In Canada, this treatment is suitable for infants aged 9 months and older, as well as children and adolescents.
• It's a way to help manage the symptoms of Morquio A syndrome and improve the patient's quality of life.

Pregnancy Risk Factor C

• Elosulfase alfa, used to treat Morquio A syndrome, has a pregnancy risk factor of C, meaning there's potential risk but benefits may still outweigh it.
• Animal studies have shown adverse effects, so caution is needed.
• Morquio A syndrome itself can pose risks to both mother and fetus.
• A pregnancy registry (MARS@bmrn.com or 1-800-983-4587) is available for women using elosulfase alfa during pregnancy to monitor any potential issues.

Elosulfase alfa use during breastfeeding:

• It's uncertain whether elosulfase alfa passes into breast milk.
• Therefore, caution is advised if it's given to nursing mothers.
• The manufacturer recommends careful consideration in such cases.
• Additionally, the pregnancy registry gathers information from women who are breastfeeding while using elosulfase alfa for treating Morquio A syndrome.

Dose in Kidney disease: 

• The manufacturer's labeling for elosulfase alfa doesn't mention any specific dosage adjustments for people with renal impairment.
• This means that individuals with kidney problems may not need to change their dose when receiving this medication.

Dose in Liver disease:

• The manufacturer's labeling for elosulfase alfa doesn't specify any dosage adjustments for individuals with hepatic (liver) impairment.
• This suggests that there may not be a need to alter the dosage based solely on liver function.

Common Side Effects of Elosulfase alfa (Vimizim):

• Central nervous system:
  • Headache
• Gastrointestinal:
  • Vomiting
  • Nausea
  • Abdominal pain
• Hypersensitivity:
  • Hypersensitivity reaction
• Miscellaneous:
  • Fever

Less Common Side Effects of Elosulfase alfa (Vimizim):

• Central nervous system:
  • Chills
  • Fatigue
• Hypersensitivity:
  • Anaphylaxis presenting as
    • Cough
    • Erythema
    • Throat tightness
    • Urticaria
    • Flushing
    • Cyanosis
    • Hypotension
    • Rash
    • Dyspnea
    • chest discomfort, and gastrointestinal symptoms
• Immunologic:
  • Immunogenicity

Contraindications to Elosulfase alfa (Vimizim):

• The manufacturer's labeling for elosulfase alfa does not list any contraindications.
• This indicates that there are no specific situations where the use of elosulfase alfa is strictly prohibited based on certain medical conditions or factors.

Warnings and precautions

Formation of antibodies:

• During clinical trials, all patients treated with elosulfase alfa developed anti-drug antibodies and neutralizing antibodies.
• However, it's unclear whether the presence of these antibodies increases the risk of infusion reactions or affects the effectiveness of treatment.
• In other words, it's unknown if having antibodies against the drug makes infusion reactions more likely or impacts how well the treatment works.

Hypersensitivity/anaphylactoid reactions: [U.S. Boxed Warning]:

• Important safety information for elosulfase alfa includes a U.S.
• Boxed Warning regarding serious hypersensitivity reactions, which can include life-threatening anaphylactic reactions.
• These reactions can occur regardless of the duration of treatment.
• Symptoms of anaphylaxis may include abdominal pain, chest discomfort, cough, cyanosis, difficulty breathing, redness of the skin, flushing, low blood pressure, nausea, rash, retching, throat tightness, hives, and vomiting.
• Patients should be closely monitored during and after infusion, and medical support should be readily available.
• Patients with acute respiratory disease are at higher risk of serious exacerbations or respiratory compromise due to hypersensitivity, so additional monitoring may be necessary.
• If an anaphylactic or acute reaction occurs, elosulfase alfa should be discontinued immediately, and patients experiencing severe or refractory reactions may require prolonged monitoring.
• Caution should be exercised when considering re-administration of the medication.

Infusion reactions

• Infusion-related reactions have been reported with elosulfase alfa, which can occur sporadically and may be severe.
• These reactions may manifest as hypersensitivity reactions, starting as early as 30 minutes from the beginning of infusion and sometimes as late as 6 days after.
• In some cases, reactions have even occurred after the 47th infusion.
• To help prevent these reactions, patients should receive premedication with antihistamines, with or without antipyretics, before the infusion.
• It's important to assess the airway before starting therapy, especially considering the potential effects of antihistamine use.
• If a reaction occurs, steps such as slowing the infusion rate, temporarily stopping the infusion, and administering additional antipyretics/antihistamines, and possibly corticosteroids may be taken.
• Treatment should be stopped immediately if a severe reaction occurs, and caution should be exercised if considering re-administration of the medication.

Acute febrile illness and respiratory disease:

• Patients with an acute febrile (feverish) or respiratory illness should be carefully evaluated before starting treatment with elosulfase alfa.
• There may be an increased risk of life-threatening complications from hypersensitivity reactions in these patients.
• Therefore, it's advisable to consider delaying treatment until the acute illness has resolved to ensure the patient's safety.

Sleep Apnea

• For patients with sleep apnea, caution is advised when using elosulfase alfa due to the potential risk of exacerbating the condition.
• Antihistamine pretreatment, which is recommended before elosulfase alfa infusion to prevent allergic reactions, may increase the risk of apneic (breathing cessation) episodes in individuals with sleep apnea.
• It's important to have apnea treatment options readily available, such as supplemental oxygen or continuous positive airway pressure (CPAP), to manage any potential respiratory issues that may arise during treatment.

Compression of the cervical cord and spinal cord:

• Patients with Mucopolysaccharidosis type IVA (MPA IVA) may develop spinal/cervical cord compression (SCC) as a result of their condition.
• It's essential to monitor these patients closely for any signs or symptoms of SCC, such as back pain, limb paralysis, urinary or fecal incontinence, or any other neurological symptoms.
• Early detection and intervention are crucial for managing SCC effectively and preventing further complications.

Monitoring parameters:

Infusion/Hypersensitivity Reactions Monitoring:

• Watch for any signs of allergic reactions during or after the infusion.
• Be alert for symptoms like difficulty breathing, chest tightness, rash, or swelling.
• Monitor for reactions even after the infusion has ended.

Spinal or Cervical Compression Symptoms:

• Keep an eye out for signs of spinal or cervical cord compression.
• Symptoms may include back pain, paralysis of limbs, or difficulty controlling urine or stool.
• Promptly report any concerning symptoms to your healthcare provider for evaluation and management.

How to administer Elosulfase alfa (Vimizim)?

• Infusion Set and Filter:
  • Use a low protein-binding infusion set with an in-line low protein-binding 0.2 micrometer filter.
• Pretreatment:
  • Administer antihistamines with or without antipyretics 30 to 60 minutes before infusion.
• Dosage for Patients <25 kg:
  • Infuse 100 mL solution at 3 mL/hour for the first 15 minutes.
  • If tolerated, increase to 6 mL/hour for the next 15 minutes.
  • Continue increasing rate by 6 mL/hour increments every 15 minutes, up to a maximum rate of 36 mL/hour.
  • Deliver the total volume of the infusion over at least 3.5 hours.
• Dosage for Patients ≥25 kg:
  • Infuse 250 mL solution at 6 mL/hour for the first 15 minutes.
  • If tolerated, increase to 12 mL/hour for the next 15 minutes.
  • Continue increasing rate by 12 mL/hour increments every 15 minutes, up to a maximum rate of 72 mL/hour.
  • Deliver the total volume of the infusion over at least 4.5 hours.
• Adjustments for Hypersensitivity Reactions:
  • Slow down, temporarily pause, or discontinue infusion if a hypersensitivity reaction occurs.
  • Immediately stop infusion if a severe reaction occurs.
• Special Considerations:
  • Do not mix with other products in the infusion tubing.
  • Complete administration within 48 hours from the time of dilution.

Mechanism of action of Elosulfase alfa (Vimizim):

• Elosulfase alfa is a synthetic version of the enzyme N-acetylgalactosamine-6-sulfatase, which is normally produced in the body.
• This enzyme is crucial for breaking down certain substances called glycosaminoglycans (GAGs), specifically keratan sulfate and chondroitin-6-sulfate.
• When there's a deficiency of this enzyme, these GAGs accumulate in tissues, leading to dysfunction at the cellular, tissue, and organ levels.
• Elosulfase alfa works by providing the missing enzyme, which is taken up by lysosomes in cells.
• This helps increase the breakdown of GAG substrates, thereby addressing the underlying cause of the disorder and potentially reducing its impact on the body.

Distribution:

• Week 0: Approximately 396 milliliters per kilogram
• Week 22: Approximately 650 milliliters per kilogram

Half-life Elimination:

• Week 0: Around 8 minutes
• Week 22: About 36 minutes

Time to Peak:

• Week 0: Takes about 172 minutes to reach peak levels
• Week 22: Takes about 202 minutes to reach peak levels

International Brand Names of Elosulfase alfa:

• Vimizim

Elosulfase alfa Brand Names in Pakistan:

No Brands Available in Pakistan.