BioMarin Pharmaceutical Inc. on Thursday released favorable data from a Phase III trial of Aryplase, an enzyme-replacement therapy for mucopolysaccharidosis-VI patients.
Also, the company said it would seek regulatory approval throughout the world early in the fourth quarter by filing a single common technical document.
BioMarin's stock (NASDAQ:BMRN) Thursday fell 8 cents to close at $6.45.
Fredric Price, chairman and CEO of Novato, Calif.-based BioMarin, told BioWorld Today the firm expects regulatory agencies to take action on the orphan drug application within a year of filing, that is, unless it is granted priority-review status, in which case the evaluation period would be shortened to six months in the U.S.
The 39-patient Phase III trial demonstrated a statistically significant improvement in endurance (p=0.025) in patients receiving Aryplase, compared to patients receiving placebo as measured by the distance walked in 12 minutes, the primary endpoint in the trial, the company said of the top-line data. (Additional details on data will be released as they are analyzed.)
"The 12-minute walk is a clinical measure, it is not a surrogate measure. It measures muscle, the cardiovascular system, endurance and, in some ways, it tries to mimic what children do on a day-to-day basis," Price said. "These kids can't walk very well, they can't feed themselves, and some can't clothe themselves."
Mucopolysaccharidosis-VI (MPS-VI), or Maroteaux-Lamy syndrome, is a genetic disease for which no therapies currently are available. It is caused by a deficiency of the enzyme human N-acetylgalactosamine 4-sulfatase, also known as arylsulfatase B, the company said.
Deficiency of the enzyme leads to the accumulation of glycosaminoglycan (GAG) in the lysosomes, giving rise to progressive cell, tissue and organ system dysfunction. Symptoms can include impaired cardiac and pulmonary function, delayed physical development, skeletal and joint deformities, impaired vision and hearing, sleep apnea and reduced endurance. The majority of patients die from disease-related complications between childhood and early adulthood, the company said.
BioMarin is experienced in getting treatments to market for rare lysosomal storage diseases, as evidenced by the FDA's approval last year of Aldurazyme, an enzyme-replacement therapy for mucopolysaccharidosis-I, partnered with Genzyme General, of Cambridge, Mass. (See BioWorld Today, May 1, 2003.)
In a conference call with analysts Thursday, Price said a majority of MPS-VI patients live in Europe.
Ronald Ellis, an analyst with Leerink Swann & Co. in Boston, estimated in a research note that there are 1,100 MPS-VI patients in the U.S. and the European Union combined. Ellis projects a product launch in the fourth quarter of 2005 with a maximum market opportunity worldwide of $220 million. The annual cost of therapy per patient likely could reach about $200,000, he said.
BioMarin owns all rights to Aryplase and expects to sell it in the U.S. with the 66-person pediatric sales force it recently gained through the $175 million acquisition of Ascent Pediatrics Inc., the pediatric business of Phoenix-based Medicis Pharmaceutical Corp. (See BioWorld Today, April 22, 2004.)
Outside the U.S., Price said the firm likely would seek a partner.
Summary data from the Aryplase Phase III trial will be presented at the 8th International Symposium on MPS and Related Diseases, held June 10-13 in Mainz, Germany, and at the 36th European Human Genetics Conference, held June 12-15 in Munich, Germany.
The Phase III was a multicenter, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of Aryplase for the treatment of MPS-VI. Patients were 5 to 29 years old and were enrolled at six sites located in the U.S., Brazil, the UK, Germany, France and Portugal.
All 38 patients who completed the trial have elected to receive Aryplase in an ongoing open-label extension study, BioMarin said.
Other data from the trial demonstrated a statistically significant reduction in GAGs excreted in the urine (p<0.001) in patients receiving Aryplase compared to patients receiving placebo. GAG reduction was one of two secondary endpoints measured in the trial.
The three-minute stair climb, another measure of endurance and also a secondary endpoint, demonstrated a positive trend (p=0.053) in patients receiving Aryplase, compared to patients receiving placebo.
Meanwhile, results of the trial indicate that treatment with Aryplase was generally well tolerated. Adverse events during infusions were more common in patients receiving Aryplase but were generally mild to moderate in nature, the company said.