Type 1 Gaucher Disease
An estimated 5,700 people in the United States are affected by type 1 Gaucher disease.1
Type 1 Gaucher disease is a rare, inherited disorder that results in the accumulation of fatty molecules, known as cerebrosides, in organs and tissues. Classified as one of the lysosomal storage disorders, type 1 Gaucher disease symptoms include enlargement of the liver and spleen (hepatomegaly and splenomegaly), and low platelet and hemoglobin
counts (thrombocytopenia and anemia).1
Type 1 Gaucher disease affects both sexes, and the condition is seen in 1-9 in 100,000 people. The disease is more prevalent in the Ashkenazi Jewish population, where the condition is seen in 1 in 600 people.1-3
Type 1 Gaucher disease is genetic and has an autosomal recessive inheritance pattern. If both parents are carriers, there is a 50% chance of the child being a carrier and a 25% chance of them having the disease.1
Causes of type 1 Gaucher Disease
Type 1 Gaucher disease is caused by mutations that disrupt the gene that controls the production of the glucocerebrosidase enzyme. The exact location of the gene is on band 21 on the long arm “q” of chromosome 1 (1q21). Different mutations of this gene are associated with the various types of Gaucher disease.4
All forms of Gaucher disease are inherited and cause disorders in lysosomal storage. As the principal digestive units in cells, lysosomes are responsible for breaking down carbohydrates and fats. In type 1 Gaucher disease this function is inhibited, and there is a lack of the enzyme glucocerebrosidase, resulting in an abnormal accumulation of glycolipids in the body.1
The age of onset of type 1 Gaucher disease ranges from childhood through adulthood. Patients affected by type 1 Gaucher disease show symptoms such as hepatosplenomegaly, anemia, thrombocytopenia, bone pain, and fractures of the femur and pelvis.1
Diagnosing type 1 Gaucher Disease
The presence of type 1 Gaucher disease may not be obvious at first. Type 1 Gaucher disease may be present in patients with unexplained anemia, easy bruising, and enlargement of the liver and spleen. The diagnosis should be confirmed through a series of specialized tests and a thorough clinical evaluation. Suggested tests include enzyme assays to measure acid beta-glucosidase activity in leukocytes or fibroblasts. The diagnosis may also be confirmed by DNA analysis for gene mutations.4
For pregnant women, prenatal diagnosis of type 1 Gaucher disease is possible through amniocentesis, where a sample of the amniotic fluid is analyzed to determine if type 1 Gaucher disease is present. Chorionic villus sampling (CVS), which involves the removal of tissue samples from a portion of the placenta, could also be carried out. These fetal cells can then be checked for reduced beta-glucosidase activity to determine if type 1 Gaucher disease is present.4
VPRIV® (velaglucerase alfa) for injection is indicated for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease.
Important Safety Information
Hypersensitivity reactions, including anaphylaxis, have occurred. The most serious adverse reactions in patients treated with VPRIV (velaglucerase alfa) for injection were hypersensitivity reactions.
Hypersensitivity reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. Patients were not routinely pre-medicated prior to infusion of VPRIV. The most commonly observed symptoms of hypersensitivity reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia. Hypersensitivity reactions in the clinical trials include any event considered related to and occurring within up to 24 hours of VPRIV infusion, including one case of anaphylaxis. Generally the reactions were mild and, in treatment-naïve patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Additional hypersensitivity reactions of chest discomfort, dyspnea, pruritus and vomiting have been reported in post-marketing experience. In some cases vomiting can be serious, requiring hospitalization and/or drug discontinuation.
As with any intravenous protein product, hypersensitivity reactions are possible, therefore, appropriate medical support, including personnel adequately trained in cardiopulmonary resuscitative measures and access to emergency measures, should be readily available when VPRIV is administered. If anaphylactic or other acute reactions occur, immediately discontinue the infusion of VPRIV and initiate the appropriate medical treatment.
Management of hypersensitivity reactions should be based on severity of the reaction, such as slowing the infusion rate, treatment with medications such as antihistamines, antipyretics and/or corticosteroids, and/or stopping and resuming treatment with increased infusion time. In cases where patients have exhibited symptoms of hypersensitivity to velaglucerase alfa or excipients in the drug product or to other enzyme replacement therapy, pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions.
The most common adverse reactions during clinical studies (in ≥10% of patients) were hypersensitivity reactions, headache, dizziness, abdominal pain, nausea, back pain, joint pain, prolonged activated partial thromboplastin time (aPTT), fatigue/asthenia, and pyrexia. In clinical studies, the overall frequency of adverse events was generally higher in the population naïve to enzyme replacement therapy (ERT) than in the population switched from imiglucerase to VPRIV.
The safety and efficacy profiles were similar in pediatric (ages 4 to 17) and adult patients. The safety of VPRIV has not been established in patients under 4 years of age. Adverse reactions more commonly seen in pediatric patients compared to adult patients include (>10% difference): rash, aPTT prolonged, and pyrexia.
The adverse reaction profile in elderly patients was consistent with that previously observed across pediatric and adult patients. In general, dose selection for an elderly patient should be approached cautiously, considering comorbid conditions. As with all therapeutic proteins, there is a potential for immunogenicity. In clinical studies, 1 of 54 (2%) enzyme treatment-naïve patients treated with VPRIV developed IgG class antibodies (neutralizing in an in vitro assay). One additional patient developed IgG antibodies to VPRIV during an extension study. It is unknown if the presence of IgG antibodies to VPRIV is associated with a higher risk of infusion reactions. Patients with an immune response to other ERTs who are switching to VPRIV should continue to be monitored for antibodies to VPRIV.
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