European Commission has granted marketing authorisation for Vpriv ( Velaglucerase alfa ), a human cell line derived enzyme replacement therapy ( ERT ) for the long-term treatment of type 1 Gaucher disease. Vpriv has been authorized as an orphan medicine through the Centralised Procedure, making it available in 30 countries across Europe.

This approval was based on data from Velaglucerase alfa clinical development programme which represents the largest and most comprehensive clinical data set supporting registration for an ERT for type 1 Gaucher disease. In total, over 100 Gaucher patients at 24 sites in 10 countries around the world participated in the clinical studies, all of which met their primary endpoints.

Across Europe, hundreds of type 1 Gaucher patients have been receiving Velaglucerase alfa through early access programmes, developed in partnership with national authorities, Gaucher expert physicians and patient associations. Globally there are over 850 patients on Velaglucerase alfa and demand continues to be strong. As a result, Shire has implemented a program to carefully monitor demand and manage requests from physicians and patients in order to ensure long-term, uninterrupted treatment with Vpriv.

Velaglucerase alfa is made using Shire's gene-activation technology, in a human cell line. Velaglucerase alfa has the exact human amino acid sequence as the endogenous glucocerebrosidase enzyme and also has a human glycosylation pattern. The safety and efficacy of Velaglucerase alfa was assessed in adults and children aged 4 years and older via a phase three program, which included Gaucher patients who switched to Velaglucerase alfa after being treated with Imiglucerase ( Cerezyme ), as well as naive patients, including an active comparison with Imiglucerase.
Vpriv was approved in the United States by the Food and Drug Administration ( FDA ) on February 26, 2010.

The most serious adverse reactions in patients treated with Velaglucerase alfa were hypersensitivity reactions.
Infusion-related reactions were the most commonly observed adverse reactions in patients treated with Vpriv in clinical studies. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia. Generally the infusion-related reactions were mild and, in treatment-naive patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Other commonly observed adverse reactions in less than 10% of patients were: abdominal pain, back pain, joint pain, upper respiratory tract infection, and activated partial thromboplastin time prolonged. Adverse reactions more commonly seen in paediatric patients ( greater than 10% difference ) included upper respiratory tract infection, rash, activated partial thromboplastin time prolonged, and pyrexia. In clinical trials one patient developed neutralizing antibodies.

Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene which results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This enzymatic deficiency causes an accumulation of glucocerebroside, primarily in macrophages. In this lysosomal storage disorder ( LSD ), clinical features are reflective of the distribution of Gaucher cells in the liver, spleen, bone marrow, and other organs. The accumulation of glucocerebrosidase in the liver and spleen leads to organomegaly. Presence of Gaucher cells in the bone marrow and spleen lead to clinically significant anemia and thrombocytopenia.
Gaucher disease is the most prevalent of the lysosomal storage disorders diseases. Gaucher disease has classically been categorized into 3 clinical types. Type 1 Gaucher disease is characterized by variability in signs, symptoms, severity, and progression. Type 1 is the most common and is distinguished from type 2 and type 3 by the lack of early neurological symptoms.

Source: Shire, 2010

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