FDA supports the safety and effectiveness of Aldurazyme for MPS I
BioMarin Pharmaceutical, based in Novato, CA, US, and Cambridge, MA, based Genzyme General, have received a complete response letter relating to the companies' marketing application for Aldurazyme (laronidase) from the FDA. Aldurazyme is an investigational enzyme replacement therapy for treatment of mucopolysaccharidosis I (MPS I), a rare, progressive and debilitating genetic disorder.
The FDA noted that the data supported the safety and effectiveness of Aldurazyme in patients with MPS I, and has not requested any additional clinical data in order to grant final approval of the drug. The companies will provide additional information to FDA on three issues outlined in the letter: post-marketing commitments, final product labeling, and completion of the manufacturing inspections process, but anticipate that these issues can be finalised in a relatively short period of time. The FDA also noted that they would work with the companies to make this important drug available to patients.
'We will respond rapidly to address the few remaining issues related to our application,' said Fredric Price, chairman and ceo of BioMarin. 'Given the serious, progressive nature of MPS I, we are heartened by the FDA's rapid review of the application. We are committed to working with the FDA and Genzyme to bring Aldurazyme to patients with MPS I as quickly as possible.'
The FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted unanimously that Aldurazyme had shown efficacy in treating MPS I, without serious safety concerns. The Agency has reviewed the companies' clinical data for Aldurazyme, which included safety and efficacy data from a Phase I/II, 10-patient, open-label trial and extension data; from a Phase III, 45-patient, randomised, double-blind, placebo controlled trial; and from the open-label extension portion of the Phase III trial.
BioMarin and Genzyme have made significant progress in recent months in preparing to launch Aldurazyme worldwide. A Marketing Authorization Application (MAA) for Aldurazyme is under review at EMEA, and the companies expect a response from them in the first quarter of 2003. The companies have submitted an application for marketing approval of Aldurazyme in Canada and Australia.
In Canada, the application was given priority review status under Health Canada's therapeutic products program. The companies also requested priority review status in Australia, where the Therapeutic Goods Administration has previously given Aldurazyme orphan drug designation.
In December 2002, BioMarin and Genzyme initiated an open-label clinical study in Europe of Aldurazyme in MPS I patients who are five years of age and younger. This study is intended to gather additional safety and efficacy data in younger MPS I patients who were not part of the Phase III study. To date, more than 70 patients have been treated with Aldurazyme as part of the clinical trials, as well as the companies' expanded access program.
Mucopolysaccharidosis I
MPS I is a life-threatening genetic disease caused by a deficiency of the enzyme alpha-L-iduronidase. This deficiency leads to the accumulation of complex carbohydrates in the lysosomes of cells, bringing about the progressive dysfunction of cellular, tissue and organ systems. Resulting symptoms can include impaired cardiac and pulmonary function, delayed physical development, skeletal and joint deformities, reduced endurance, and in some cases, delayed mental function. A majority of patients die before adulthood from complications of the disease.