Washington Editor

Genzyme General and its partner, BioMarin Pharmaceutical Inc., received FDA approval for Aldurazyme, an enzyme replacement therapy for the treatment of a rare degenerative disease, mucopolysaccharidosis-1.

Aldurazyme is Genzyme's third FDA-approved enzyme replacement therapy. Just last week, the company received approval of Fabrazyme for Fabry's disease. The other is Cerezyme, for Gaucher's disease.

For BioMarin, of Novato, Calif., FDA approval triggers the only milestone in the partnership, a $12.1 million payment from Genzyme General, a division of Genzyme Corp., of Cambridge, Mass. The companies entered a 50-50 partnership to develop Aldurazyme in 1998, and as part of that worldwide deal, Genzyme will sell Aldurazyme and BioMarin will manufacture it. (See BioWorld Today, Sept. 16, 1998.)

"This really marks the beginning of a transformation of BioMarin from a purely development company to one that is now commercially oriented," Fredric Price, chairman and CEO of BioMarin, told BioWorld Today. "Obviously, we continue with our development program full blast, but we now have a commercial hat on, and so that is going to drive the organization in terms of the kinds of people we hire, the kinds of facilities we build and how we are going to start thinking about our own commercial needs."

Genzyme is riding high after the recent rush of good news, but following favorable panel hearings for both Aldurazyme and Fabrazyme in January, positive FDA outcomes were expected. Both products received orphan status, which guarantees seven-year market exclusivity. (See BioWorld Today, Jan. 14, 2003, and Jan. 16, 2003.) BioMarin's stock (NASDAQ:BMRN) Wednesday closed at $10.98 down 77 cents, while Genzyme's stock (NASDAQ:GENZ) closed at $40.27, down 43 cents.

"It's obviously unprecedented in the biotech industry to have two products approved within a week of each other, so it is very exciting for us in both cases," Dan Quinn, Genzyme's spokesman, told BioWorld Today. "These drugs are for very needy patient populations, so we are just extremely fortunate and excited to be providing treatment for people who desperately need it."

Indeed, there's nothing on the market to treat the genetic disease that affects an estimated 3,000 to 4,000 people worldwide (about 1,000 in the U.S.). Mucopolysaccharidosis-1, or MPS-I, is caused by a deficiency of the enzyme alpha L-iduronidase, which leads to the accumulation of complex carbohydrates in the lysosomes of cells. Resulting symptoms can include impaired cardiac and pulmonary function, delayed physical development, skeletal and joint deformities, reduced endurance and, in some cases, delayed mental function. Patients often die before reaching adulthood.

Aldurazyme (laronidase) is indicated for patients with the Hurler and Hurler-Scheie forms of MPS-I, and for Scheie patients with moderate to severe symptoms.

Quinn said the company hopes to launch Aldurazyme within the next three weeks. Genzyme already employs 37 sales people schooled in enzyme replacement therapy who have been selling Cerezyme. Fabrazyme also is expected to be launched within weeks.

As for price, Quinn said the company isn't ready to release an estimate. However, in a research note released in advance of the FDA panel meeting, Yaron Werber, vice president and biotechnology analyst at S.G. Cowen Securities Corp., of New York, estimated the U.S. market at $175 million, based on a cost of $175,000 per year per patient. The worldwide estimate is $525 million annually. Last week company officials said Fabrazyme is expected to cost $180,000 per year per patient, and Cerezyme costs about $150,000 to $175,000.

European officials issued a favorable opinion on Aldurazyme in February, leaving the companies to anticipate approval in the first half of this year.

The biologics license application was based on a six-month, randomized, placebo-controlled Phase III study (also called ADIL-003) of 45 patients.

Clinical trials demonstrated that Aldurazyme could provide clinically important benefits for patients, including pulmonary function and walking ability. Aldurazyme also has been shown to be effective at reducing the excess carbohydrates stored in the organs of patients with MPS-I, providing evidence that the enzyme is effective at a biochemical level, the companies said.

As part of the approval, the companies have agreed to a number of post-marketing commitments. They will complete a previously announced study initiated in December 2002 to evaluate the safety and pharmacokinetics of Aldurazyme in patients less than 5 years of age. Also, they will conduct an open-label dose optimization study in about 32 patients, and continue the Phase III extension study for a total of four years from study initiation. In a registry setting, the company also will obtain long-term information related to the natural history of MPS-I and the safety and efficacy of Aldurazyme.