BioMarin Pharmaceutical Inc. said enrollment will begin shortly in a Phase III trial of its second enzyme replacement product, Aryplase, for muccopolysaccarhidosis-VI, or Maroteaux-Lamy syndrome.
"We're expecting to enroll patients in the next couple of weeks," said Joshua Grass, manager of investor relations for Novato, Calif.-based BioMarin. If all goes well, "we could have another drug on the market in 2005," he added.
The six-month, randomized, double-blind, placebo-controlled trial will test Aryplase in 36 patients at six international sites.
"We're pleased with the design," Grass said. "We've seen encouraging results [in earlier trials] with the 12-minute walk and the secondary endpoints we're measuring."
The Phase III trial's primary endpoint will be the change in endurance compared to placebo as measured by the distance walked in the 12-minute walk test.
Secondary endpoints will include the change in urinary glycosaminoglycan excretion, which is a measure of the biochemical activity of the enzyme, and the change in the number of stairs climbed in three minutes.
The company will infuse patients with a dose of 1.0 mg/kg, expecting to complete the double-blind part of the study in about nine months. After the six-month, placebo-controlled part of the trial, patients receiving placebo will receive weekly infusions of Aryplase (recombinant human arylsulfatase B).
Given positive data from the double-blind portion of the trial, BioMarin plans to file applications to market Aryplase in the U.S. and European Union in the second half of 2004.
With partner Genzyme General, of Cambridge, Mass., BioMarin recently won FDA approval for Aldurazyme, an enzyme replacement therapy for mucopolysaccharidosis-1. Leerink Swann & Co., of Boston, predicts Aldurazyme will sell $12.1 million in 2003, with BioMarin gaining profitability in 2005. (See BioWorld Today, May 1, 2003.)
"From our perspective everything is going well" with the launch of Aldurazyme, Grass told BioWorld Today. Genzyme "seems like they're doing all the things they should be doing," he added.
"This is not like dropping off pills to a primary-care physician," he said. "It takes a while for infusion sites to get set up and for patients and their families to arrange their lives around it."
Genzyme recently won approval of its enzyme replacement therapy Fabrazyme (agalsidase beta) for Fabry's disease, and so will be launching two drugs at once. Dan Quinn, associate director of public relations for Genzyme, said the company has "increased the size of our sales force to a point where we're quite comfortable with our ability to launch both of these drugs simultaneously."
Although a separate sales force was not dedicated to Aldurazyme, the force includes about 40 salespeople in the U.S., with a separate team in Europe, he said. The same force markets Cerezyme (imiglucerase), Genzyme's enzyme-replacement therapy for Gaucher's disease.
"With Aldurazyme [unlike Fabrazyme], there is a large number of pediatricians who are seen," Quinn said. "But there's some overlap" in the customer base, he added.
The FDA and European regulators are requiring postmarketing studies for Aldurazyme in 100 patients, which could take away from the pool of about 750 MPS-I patients identified so far, Quinn acknowledged, although some of the patients in the postmarketing study also could be paying.
"It's unclear how that's going to break down," he told BioWorld Today. "All that we've given for the rest of this year is the $10 million to $13 million figure [in Aldurazyme sales] and that certainly accounts for patients in postmarketing studies."
There are "some caveats" on the estimate of eligible MPS-I patients, mainly related to the patient registries used to compile it, but Quinn called the estimate "reasonable."
BioMarin also has in Phase III trials Neutralase, a carbohydrate-modifying enzyme that cleaves heparin, for the reversal of anticoagulation by heparin in coronary arterial bypass grafting surgery. BioMarin has worldwide rights to it, and last month raised $125 million through a private placement of convertible subordinated notes due 2008 in order to increase the number of trial sites. (See BioWorld Today, June 18, 2003.)
The company's stock (NASDAQ:BMRN) closed Monday at $9.88, up 18 cents.