BioMarin Pharmaceutical Inc and Genzyme General has released additional data from their ongoing open-label Phase III extension study of Aldurazyme (laronidase), an investigational drug for the treatment of mucopolysaccharidosis I (MPS I).
The companies released data regarding the study's two primary endpoints: pulmonary function as measured by percent predicted Forced Vital Capacity (FVC); and endurance as measured by distance covered in the six-minute walk test. Measurements of these endpoints were taken 36 weeks after the commencement of the open-label extension study, or a total of 62 weeks after commencement of the placebo-controlled trial. This new data has recently been submitted to the U.S. Food and Drug Administration (FDA) for review as part of the Biologics License Application (BLA) that was submitted on July 26, 2002. The data will also be submitted to the European Agency for the Evaluation of Medicinal Products (EMEA).
The 22 patients who received Aldurazyme for 62 weeks demonstrated a mean FVC change of +5.4 percentage points compared to pre-treatment baseline. In the six-minute walk test, these patients had a mean +40.0 meter change from pre-treatment baseline. For both the FVC and the six-minute walk tests, these results indicate that patients maintained the improvements observed after 50 weeks of Aldurazyme treatment.
After 36 weeks, the 23 patients who received placebo during the placebo-controlled portion of the trial demonstrated a mean +2.6 percentage point increase in FVC from their pre-Aldurazyme treatment baseline. Most of the improvement was observed between Weeks 25 and 36 of the open-label extension study. In the six-minute walk test, these patients demonstrated a mean +32.4 meter change from pre-treatment baseline, an increase in the improvement observed following 24 weeks of Aldurazyme treatment.
The safety profile in the extension study has been comparable to the double-blind period. The most commonly reported adverse events were headache, rhinitis, and pharyngitis. As previously reported, one patient in the extension study died of causes considered by the principal investigator to be unrelated to Aldurazyme.
On October 28, 2002, BioMarin and Genzyme announced that the FDA notified the companies that the BLA for Aldurazyme will be reviewed by the FDA's Endocrinologic and Metabolic Drugs Advisory Committee on January 15, 2003. On September 13, 2002, the FDA granted the Aldurazyme BLA 6-month priority review status. As a result, the companies anticipate a response from the FDA at the end of January 2003. The Marketing Authorization Application (MAA) for Aldurazyme is under review by the European Agency for the EMEA; the companies expect a response from EMEA in the first half of 2003.
MPS I is a progressive, debilitating and fatal 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, leading to the progressive dysfunction of cellular, tissue and organ systems. Resulting symptoms, which span a spectrum of severity, 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.
Aldurazyme is an investigational enzyme replacement therapy for patients with MPS I, a disease for which no specific drug treatments currently exist.
BioMarin and Genzyme formed a joint venture in 1998 to develop and commercialize Aldurazyme worldwide. Under the terms of the joint venture, if approved for commercial sale, BioMarin will manufacture Aldurazyme and Genzyme will have responsibility for the commercialization of the product. The companies have obtained Orphan Drug designation and Fast Track status for Aldurazyme for the treatment of MPS I from the FDA and orphan medicinal product designation from the EMEA.