By Randall Osborne
Pushing toward the market with its enzyme-replacement therapy for a rare but potentially fatal disease that strikes children, BioMarin Pharmaceutical Inc. plans a joint venture with Genzyme Corp. to develop and commercialize the treatment.
"We expect it will be completed this summer," said Grant Denison, chairman and CEO of Novato, Calif.-based BioMarin. A new drug application will be filed in the third quarter, he added.
Genzyme already sells a similar therapy for a different disease.
BioMarin's drug, its lead product, is L-iduronidase, a recombinant enzyme designed to treat mucopolysaccharidosis I (MPS I), a genetic disorder of which the best known and most severe form is Hurler syndrome.
BioMarin and Genzyme expect to duplicate the success of Cerezyme (recombinant glucocerebrosidase), Genzyme's treatment for Gaucher's disease, which also is related to an enzyme deficiency.
"There are 30 different enzymes, any one of which could be missing, but you've got to nail the right enzyme," Denison said.
Genzyme earns more than $300 million annually in sales of Cerezyme and Ceredase, the natural version of the enzyme, derived from human placenta.
Like Gaucher's disease — characterized by liver and spleen enlargement, with bone weakening — MPS I is rare. The condition causes carbohydrate materials to build up in all parts of the body. Symptoms of MPS I include enlargement of the liver and spleen, skeletal deformity, vision impairment, stunted growth, hearing loss and fluid on the brain.
MPS I afflicts more than 1,000 patients, primarily children, in the developed world.
"It's terrible," Denison said. "I know these patients. I know their families." The first patient in the 10-patient trial is 17 years old. At the start of treatment, he was "so crippled he couldn't stand up, and now he's three and a half inches taller because he can stand up straight," Denison said.
Although the FDA calls the trial begun in January a "pivotal Phase I study," it is essentially Phase I, II and III trials rolled into one, he said.
"It's unblinded, and we're treating sick kids," Denison said. "The trial duration is six months, but they'll be on it for the rest of their lives."
The trial will reach its six-month point in July or August. "We'll keep it going, because we want long-term data," he added.
Last September, the FDA granted L-iduronidase orphan drug status, which allows for exclusive marketing of the product for seven years after approval.
"We anticipate an expedited review," Denison said.
Although MPS I is "severely under-diagnosed," about 3,000 known patients could use BioMarin's drug worldwide. The Gaucher's disease enzyme treatment is used by about 2,500.
Development of the MPS I drug "looks like the Genzyme model," Denison said.
Treatment will be expensive, he conceded, but the disease already takes a heavy monetary toll.
"These Hurler's kids routinely cost a couple million dollars to manage medically over the course of their lives," he said. They require spinal surgeries, cataract treatments and heart valve repairs, along with recurrent hospitalizations because of infections.
Denison said BioMarin is working on "several" other enzyme-replacement treatments, but declined to be more specific. "I expect we'll have some announcements before the end of the year," he said.
Earlier this year, BioMarin raised $10 million in a round of private financing. The company's joint-venture deal is with Genzyme General, one of three divisions of Cambridge, Mass.-based Genzyme. (See BioWorld Today, Jan. 28, 1998, p. 1.)
BioMarin is privately held. Genzyme's stock (NASDAQ:GENZ) closed Wednesday at $26.50, up $0.375. *