Rare diseases: important safety information on Elosulfase alfa for Morquio A syndrome


Vimizim ( Elosulfase alfa ) is the first enzyme replacement therapy ( ERT ) designed to target the underlying cause of Morquio A syndrome, a deficiency in the enzyme N-acetylgalactosamine-6 sulfatase ( GALNS ).
Vimizim is intended to provide the exogenous enzyme GALNS that will be taken up into the lysosomes and increase the catabolism of GAGs.

Morquio A syndrome, or mucopolysaccharidosis IVA ( MPS IVA ) is a rare disease in which people are missing an enzyme that is essential in the breakdown and removal of the glycosaminoglycans ( GAGs ) called keratan sulfate ( KS ) and chondroitin-6-sulfate ( C6S ). The incompletely broken down GAGs remain stored in cells in the body causing progressive damage. This excessive storage causes systemic skeletal dysplasia, short stature, and joint abnormalities, which limit mobility and endurance.
Malformation of the chest impairs respiratory function, and looseness of joints in the neck cause spinal instability and potentially spinal cord compression.
Other symptoms may include hearing loss, corneal clouding, and heart disease.
Initial symptoms often become evident in the first five years of life.
The disease substantially limits both the quality and length of life of those affected. The rate of incidence of Morquio A syndrome is as yet unconfirmed and varies among different populations, and estimates vary between 1 in 200,000 live births and 1 in 450,000 live births.

Life-threatening allergic reactions, known as anaphylaxis, can occur during Elosulfase alfa infusions. Due to the potential for anaphylaxis, appropriate medical support should be readily available when Elosulfase alfa is administered and for an appropriate period of time following administration.

Hypersensitivity reactions have been observed as early as 30 minutes from the start of infusion but as late as six days after infusion. Frequent symptoms of hypersensitivity reactions included anaphylactic reactions, urticaria, peripheral edema, cough, dyspnea, and flushing.

Because of the potential for hypersensitivity reactions, administer antihistamines with or without antipyretics prior to infusion. If severe hypersensitivity reactions occur, immediately stop the infusion of Elosulfase alfa and initiate appropriate treatment. Patients with acute febrile or respiratory illness at the time of Elosulfase alfa infusion may be at higher risk of life-threatening complications from hypersensitivity reactions.

Sleep apnea is common in MPS IVA patients. Evaluation of airway patency should be considered prior to initiation of treatment with Elosulfase alfa.
Patients using supplemental oxygen or continuous positive airway pressure ( CPAP ) during sleep should have these treatments readily available during infusion in the event of an acute reaction, or extreme drowsiness/sleep induced by antihistamine use.

Spinal or cervical cord compression ( SCC ) is a known and serious complication of MPS IVA and may occur as part of the natural history of the disease.
In clinical trials, SCC was observed both in patients receiving Elosulfase alfa and patients receiving placebo. Patients with MPS IVA should be monitored for signs and symptoms of SCC ( including back pain, paralysis of limbs below the level of compression, urinary and fecal incontinence ) and given appropriate clinical care.

All patients treated with Elosulfase alfa 2 mg/kg once per week in the placebo-controlled trial developed anti-drug antibodies.

Elosulfase alfa should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Elosulfase alfa is present in human milk.

Safety and effectiveness in pediatric patients below 5 years of age have not been established.

In clinical trials, the most common adverse reactions ( greater than or equal to 10% ) occurring during infusion included pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue.
The acute reactions requiring intervention were managed by either temporarily interrupting or discontinuing infusion, and administering additional antihistamine, antipyretics, or corticosteroids. ( Xagena )

Source: BioMarin, 2014

XagenaMedicine_2014



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