US FDA speeds up review for velaglucerase alfa to treat Gaucher disease: Shire

Velaglucerase alfa, an enzyme replacement therapy in development for the treatment of Type 1 Gaucher disease, has been granted priority review by the United States Food and Drug Administration, maker of the drug Shire plc announced.

Velaglucerase alfa will get speedier approval because of the reduced review timing from  Priority Review designation.

Priority Review designation accelerates the target review timing from ten to six months and is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists.

For velaglucerase alfa, US FDA has issued an action date for the new drug application (NDA) of February 28, 2010 under the Prescription Drug User Fee Act (PDUFA).

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, skeleton, and lungs.

The accumulation of glucocerebrosidase in the liver and spleen leads to organomegaly. Bone involvement results in skeletal abnormalities and deformities as well as bone pain crises.

Deposits in the bone marrow and splenic sequestration lead to clinically significant anemia and thrombocytopenia.

Gaucher disease is the most prevalent lysosomal storage disorder, with an incidence of about 1 in 20,000 live births.

Gaucher disease has classically been categorized into 3 clinical types. Type 1 is the most common; it is distinguished from Type 2 and Type 3 by the lack of central nervous system involvement.

Type 1 Gaucher disease is characterized by variability in signs, symptoms, severity, and progression.

Velaglucerase alfa supplements or replaces beta-glucocerebrosidase, the enzyme that catalyzes the hydrolysis of glucocerebroside, reducing the amount of accumulated glucocerebroside and correcting the pathophysiology of Gaucher disease.

Velaglucerase alfa program included the largest and most comprehensive set of Phase III clinical trials conducted to date for Gaucher disease, Shire said.

Over 100 patients at 24 sites in 10 countries around the world have participated the clinical studies using velaglucerase alfa.

Shire study using Velaglucerase alfa was a 12-month switch study in 40 clinically stable Type 1 Gaucher patients aged two years and older who had been receiving treatment with imiglucerase at doses ranging between 15 U/kg and 60 U/kg every other week for a minimum of 30 consecutive months.

This study assessed the safety of patients switched from imiglucerase to velaglucerase alfa administered at the same number of units as their imiglucerase dose. In this study, hemoglobin concentrations, platelet counts, and organ volumes were sustained through 12-months of velaglucerase alfa treatment, and the therapy was generally well-tolerated.

Velaglucerase alfa is made using Shire’s proprietary technology, in a human cell line. The enzyme produced has the exact human amino acid sequence and has a human glycosylation pattern.

In the U.S., patients continue to be enrolled in an FDA-approved treatment protocol, under which Gaucher patients receive velaglucerase alfa prior to commercialization.

Shire has also engaged with national and regional authorities outside the U.S. and patients are receiving velaglucerase alfa through pre-approval access programs.

Shire plans to file the Marketing Authorization Application (MAA) Velaglucerase alfain the EU for 2009.

Shire is a specialty pharmaceutical company focusing on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases.