BioMarin Pharmaceutical Inc. moved Aryplase (galsulfase) into the FDA's hands, filing for approval of the enzyme-replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI), an inherited and life-threatening disease for which no drug therapies are available.
The Novato, Calif.-based company submitted its biologics license application based on feedback from a September meeting with the agency. The fully electronic filing includes a set of preclinical, clinical and manufacturing-related information on Aryplase.
"The company is very excited to get the BLA filed," Joshua Grass, BioMarin's senior manager of investor and financial relations, told BioWorld Today. "It's been years in the making."
Among findings underlying the submission are data from a Phase III trial that met its primary endpoint, showing that use of the drug produced a statistically significant improvement in endurance, compared to placebo, as measured by the distance walked in 12 minutes (p=0.025). (See BioWorld Today, June 4, 2004.)
Secondary endpoints were a statistically significant reduction in glycosaminoglycans excreted in the urine (p<0.001) in patients receiving Aryplase compared to placebo, and a three-minute stair climb demonstrated a positive trend (p=0.053) in patients receiving Aryplase compared to placebo. The trial involved 39 patients.
Also as part of the submission, BioMarin requested priority review. If the FDA accepts the application and grants the priority-review request, it is expected to complete its review and take action within six months.
"We don't know of any other treatments in development for MPS VI," Grass said, adding that Aryplase has received fast-track status and orphan drug designation for the condition, a disease also known as Maroteaux-Lamy syndrome. It is caused by the deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B), a lysosomal enzyme required for the breakdown of glycosaminoglycans. Most MPS VI patients die from disease-related complications between childhood and early adulthood.
Aryplase is designed to address the underlying deficiency of MPS VI, which is closely related to MPS I, and provide the enzyme that MPS VI patients lack. Grass said the company's experience in getting Aldurazyme (laronidase) to market, in partnership with Cambridge, Mass.-based Genzyme Corp., has proved helpful in advancing Aryplase into the regulatory space.
BioMarin said it plans to file for European approval by the end of the year. The company owns all rights to Aryplase and expects to sell it in the U.S. with a pediatric sales force acquired earlier this year through a $175 million purchase of Ascent Pediatrics Inc., the pediatric business of Phoenix-based Medicis Pharmaceutical Corp. In Europe, BioMarin expects to partner the product, and talks are under way. (See BioWorld Today, April 22, 2004.)
Grass said enzyme-replacement therapies typically cost about $200,000 per year, but a price has not yet been fixed to Aryplase. Worldwide, the company has estimated there are about 1,100 MPS VI patients in developed countries. It has identified about 250.
"It usually takes a fair amount of time to get fair but steady growth," Grass added. "Once there is a drug available for a disease, the awareness of the disease tends to increase."
Elsewhere in its portfolio, BioMarin markets Orapred, a children's asthma drug brought on board through the Ascent acquisition. Clinical research efforts are focused in part on Phenoptin, a product nearing Phase II for phenylketonuria, and Vibrilase, which recently completed a Phase Ib study to test its ability to treat burns. The company last week entered a deal for Phenoptin's Japanese rights with Daiichi Suntory Pharma Co. Ltd., of Tokyo. (See BioWorld Today, Nov. 29, 2004.)
On Monday, BioMarin's stock (NASDAQ:BMRN) gained 38 cents to close at $5.03.