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REPLAGAL® is a human cell line derived enzyme replacement therapy (ERT) indicated for the long term treatment of patients with Fabry disease. REPLAGAL® aims to address the underlying cause of Fabry disease, by replacing deficient or missing enzyme with active enzyme to stop or ameliorate the clinical manifestations of the disease, such as halting the decline and preserve renal function, improve cardiac abnormalities, reduce pain, improve gastro-intestinal symptoms and significantly improve quality of life. The active substance in REPLAGAL® is agalsidase alfa (a-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 a-galactosidase. It is produced by switching on the gene for a-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 REPLAGAL® is administered by a 40 minute low volume intravenous infusion on a fortnightly (bi-weekly) basis. It is approved in 37 countries and is marketed by Shire Human Genetic Therapies, a subsidiary of Shire plc. Who can be treated with REPLAGAL® (agalsidase alfa)? 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. Fabry disease is a progressive, X-linked genetic disorder resulting from a defect in the gene for the lysosomal enzyme alpha-galactosidase A (alpha-GAL). While Fabry is a rare disease — the incidence is estimated to be 1 in 40,000 males — it is found among all ethnicities.[1] Despite being an X-linked disorder, some females may express varying degrees of clinical manifestations. Moreover, there are variants of Fabry disease that do not present with classical signs and symptoms. This suggests that the actual incidence of Fabry disease may be higher than currently estimated. Since Fabry disease was first described in 1898, much has been learned about its diagnosis, progression, and management. 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 Fabry Disease. The active substance in Replagal® is agalsidase alfa (1mg/ml). Agalsidase alfa is a form of the human enzyme a-galactosidase. It is produced by switching on the gene for a-galactosidase A in cells. The enzyme is then removed from the cells and made into a sterile concentrate for solution for infusion. REPLAGAL
Replagal (力甫盖素浓缩注射液) 剂量：
About Fabry Disease Background: Fabry disease is an X-linked lysosomal storage disease that is caused by deficient activity of lysosomal enzyme a-galactosidase A (a-Gal A). Most males with no a-Gal A activity develop the classic phenotype of Fabry disease, which affects multiple organ systems. The first clinical manifestations of the disease, which consist of episodes of severe pain in the extremities (acroparesthesias), hypohidrosis, corneal and lenticular changes, and skin lesions (angiokeratoma) develop in childhood. The rate of disease progression and specific organ damage demonstrate intrafamilial and interfamilial variability. Renal failure, cardiovascular disease, and stroke are the major causes of morbidity and mortality, occurring in the fourth or fifth decade of life. Pathophysiology: Glycosphingolipids, predominantly globotriaosylceramide (GL-3) and galabiosylceramide, accumulate in the lysosomes of various cells (eg, in the vascular endothelium of multiple organs) owing to a-Gal A deficiency. The accumulation of GL-3 in the lysosomes causes lysosomal and cellular dysfunction; this, in turn, triggers the cascade of cells and tissue ischemia and fibrosis. Frequency: In the US: Fabry disease is one of the more common lysosomal storage disorders, affecting approximately 1 in 40,000-60,000 males. Mortality/Morbidity: Prior to the availability of renal transplant, dialysis, and, more recently, enzyme replacement therapy (ERT), the average age at death in men with classic Fabry disease was 41 years. Renal failure, heart failure and/or myocardial infarction, and stroke were among the most likely causes of death. Race: Although most patients with Fabry disease are white, the disorder has been described in patients in many ethnic groups, including those with Hispanic, African, Asian, and Middle Eastern ancestry. Sex: As is expected in X-linked disorders, males with deleterious mutations have little-to-no residual a-Gal A activity. Therefore, these patients experience the full spectrum of disease symptoms. Because of random X inactivation (lyonization), the disease presentation in female carriers is more variable and depends on the normal-to-mutant ratio of a-Gal A in the different tissues. A significant number of female carriers may develop Fabry disease–related symptoms, including acroparesthesias, GI symptoms, renal and cardiac disease, and/or stroke. Age: Most males with classic Fabry disease first manifest symptoms in childhood or early adolescence. The earliest manifestations include acroparesthesias, angiokeratomas, hypohidrosis, and lenticular and corneal changes. Proteinuria usually becomes evident in the second decade of life, and renal insufficiency is typically present in the third decade of life. Cardiovascular and cerebrovascular diseases usually develop in the fourth decade of life. Individuals with atypical renal or cardiac variants usually do not have signs or symptoms in childhood. Many of these patients remain asymptomatic well into adulthood, when patients with classic symptoms are severely affected or have died from the disease. Symptoms: Not sweating, fatigue, red spots on skin. Some of the most common pathological symptoms includes skin lesions (angiokeratomas), and a burning pain of the extremities. This pain can become very intense, especially when one has a fever. Angiokeratomas are tiny, painless papules that appear at any region of the body, but are predominant on the thighs, buttocks, lower abdomen, and groin. Ocular involvement may be present showing cornea verticillata (also known as vortex keratopathy); this corneal whorling does not have any effect on vision or eye function. Symptoms are typically first experienced in early childhood and can be very difficult to understand; the rarity of Fabry disease to many clinicians sometimes leads to misdiagnoses or ignorance. Manifestations of the disease usually increase in number and severity as an individual ages. Kidney complications are a common and serious effect of the disease; renal insufficiency and renal failure may worsen throughout life. Proteinuria is often the first sign of kidney involvement. Cardiac complications occur when Gb3 builds up in different heart cells; heart related effects worsen with age and may lead to increased risk of heart disease. Cerebrovascular effects lead to an increased risk of stroke. Other symptoms include an inability or decreased ability to sweat, fatigue, ringing in the ears (tinnitus), vertigo, nausea, and diarrhea. Fabry's disease may also have ocular involvement, such as the presence of corneal verticillata in the basal layers of the epithelium, conjunctival aneursyms, and spokelike cataracts. Papilledema, macular edema, optic atrophy and retinal vascular dilation may also be present. What are some other names used for Fabry Disease?: Alpha-galactosidase A deficiency |
