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Contact: Regulatory Affairs Division
Conditional Approval of Replagal™ (agalsidase alfa)
The active substance in Replagal is agalsidase alfa (α-galactosidase A) (1mg/mL). The other ingredients are polysorbate 20, sodium chloride, sodium hydroxide, sodium phosphate monobasic monohydrate and water for injections.
Agalsidase alfa is a form of the human enzyme α-galactosidase. It is produced by switching on the gene for α-galatosidase A in cells. The enzyme is produced from human cells and made into a sterile concentrate for solution to be mixed with normal saline for infusion.
Replagal is a concentrate for solution for infusion. Each vial contains 3.5 mg of agalsidase alfa. Before Replagal is given it is mixed with 100 mL of 9 mg/mL (0.9%) sodium chloride intravenous solution. The prepared solution will be infused into a vein over a 40 minute period.
Health Canada has approved Replagal (agalsidase alfa) with conditions, under the Notice of Compliance with Conditions policy. This authorization reflects the promising nature of the clinical evidence which must be verified and/or extended with further studies. Products approved under Health Canada's NOC/c policy, have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment.
Replagal is used to treat Fabry Disease. It is used as enzyme replacement therapy when the level of enzyme in the body is lower than normal as in males with Fabry Disease.
Fabry disease is a rare lysosomal storage disorder caused by deficient activity of the enzyme, alpha-galactosidase A (α-gal). Without α-gal, the lipid globotriaosylceramide (Gb3) also referred to as ceramidetrihexoside (CTH), accumulates in lysosomes throughout the body and impairs the function of several major organs including the kidney and heart. Fabry disease occurs in all ethnic groups and is an X-linked genetic trait affecting primarily males, although females may be severely affected by the disease. Due to its rarity and vast array of symptoms, diagnosis is often difficult and usually occurs as late as the second decade of life. Commonly, patients are misdiagnosed and often visit a variety of medical specialists.
Agalsidase alfa enables the breakdown of Gb3. Treatment with the enzyme has been shown to reduce accumulation of Gb3 in many cell types including cells that line blood vessels, tissues and organs.
At present there is no specific curative treatment for the condition and patient management is limited to symptom control and supportive measures. Patients with Fabry Disease are at risk for the loss of kidney function resulting in the need for dialysis or transplantation.
Patients should not take Replagal if they are allergic (hypersensitive) to agalsidase alfa or any of the other ingredients of Replagal.
Approximately 10% of patients had reactions during or within one hour following infusion of Replagal. Most reactions were mild. The most common symptoms were chills and facial flushing (warmth and redness). These reactions have generally first happened 2 - 4 months after the start of treatment and decreased over time. Most of the time you can still be given Replagal even if the symptoms occur.
If you experience an allergic side effect following the administration of Replagal, you should immediately contact your doctor.
If symptoms occur during your infusion:
It is possible that treatment with Replagal will make your body produce antibodies.
If severe allergic (anaphylactic-type) reactions occur, immediate discontinuation of the administration of Replagal may be considered and an appropriate treatment will have to be initiated by your doctor.
Like all medicines, Replagal can have side effects. Most side effects are mild to moderate and include headache, tingling, numbness, tremors, fatigue, change in temperature sensation, increased blood pressure, upset stomach, diarrhea, coughing, sore throat, difficulty sleeping, change in the taste of food, change in smell, difficulty speaking, acne, dry skin and eye problems. About 1 out of 10 patients may have a reaction during or shortly after infusion of Replagal. These effects include chills and facial flushing (warmth and redness). However some effects may be serious and may need treatment.
Tell your doctor immediately if you notice any of these effects which may be serious:
Tell your doctor as soon as possible if you notice any of the following:
If you notice any side effects not mentioned above, please inform your doctor.
Replagal is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry Disease (alpha-galactosidase A deficiency). Replagal has been found to be safe and well tolerated following 12 months of therapy in children with Fabry disease and there is no evidence of any difference in the safety profile compared to the larger experience in treating adult patients. In the first six children studied there have been no reports of significant infusion related symptoms and no patients have developed IgG anti-agalsidase alfa antibodies following 12 months of therapy. Studies in patients over the age of 65 have not been performed.
Replagal treatment should initially be supervised by a physician experienced in the management of patients with Fabry Disease or other inherited metabolic diseases.
Replagal is intended for long term, chronic use under the guidance and supervision of a physician. Home infusion has been safely performed.
Replagal has to be diluted in 100 mL of 9 mg/mL (0.9%) sodium chloride solution before use. After dilution Replagal is given in a vein (usually in an arm vein).
The dose is an infusion of 0.2 mg for every kg of the patient's body weight. The infusion will be given every two weeks. Studies are underway to evaluate more frequent and/or higher doses of Replagal therapy than used in clinical trials to date.
All patient medical inquiries regarding Replagal should be directed to our Medical Information Department located at Paladin Labs Inc. at 1-888-550-6060.
This document along with the Replagal Prescribing Information and Patient Information can be found on our website at www.tktx.com