Staff Writer

As it prepares to move Phenoptin into Phase II trials, BioMarin Pharmaceutical Inc. entered a partnership with Daiichi Suntory Pharma Co. Ltd.

Novato, Calif.-based BioMarin not only will exclusively receive extensive preclinical and clinical data on 6R-BH4, or tetrahydrobiopterin, the active ingredient in Phenoptin, but the company also gains access to commercial-grade 6R-BH4. In return, Daiichi gets the rights to market Phenoptin for phenylketonuria (PKU) in Japan.

"It allows us to move the program forward faster than if we had not done this deal," said Joshua Grass, BioMarin's senior manager of investor and financial relations.

BioMarin intends to begin a Phase II trial of the product in PKU by the end of this year. And depending on discussions with the FDA, it could move into Phase III trials in 2005. The company filed in August the investigational new drug application, which included Daiichi's data on 6R-BH4. In addition to gaining Japanese rights to Phenoptin in PKU, Daiichi is entitled to approval milestone payments and royalties on sales of Phenoptin outside of Japan. Other financial details were not disclosed.

Tokyo-based Daiichi manufactures its own formulation of 6R-BH4, which is approved in Japan to treat the genetic disease, BH4-deficiency.

"They're actually able to make it for a lower cost, and that's going to be helpful for us going forward because it's a difficult drug to make," Grass told BioWorld Today. "The fact that they're already making it in a commercial process is extraordinarily helpful."

In July, BioMarin announced positive results from a pilot study of 6R-BH4 in 20 patients with PKU, showing it can lower blood phenylalanine levels and might allow patients to relax or eliminate their restrictive, protein-free diets. The open-label study was conducted at two sites in the U.S., and patients were given 10-mg/kg oral doses of 6R-BH4 daily for seven days. Phenoptin, an oral enzyme cofactor, has orphan drug status in the U.S. and Europe.

Pheynlketonuria is a genetic disease that affects 50,000 children in the developed world. It is characterized by the lack of phenylalanine hydroxylase, an enzyme needed to metabolize phenylalanine (Phe), an amino acid found in most protein-containing foods. Without the enzyme, Phe accumulates in the blood, resulting in complications such as severe mental retardation and brain damage.

Newborn babies are screened for PKU, and those diagnosed with the disease must follow a strict diet.

"In adolescents, the diet becomes more difficult to comply with," Grass said. "This is not like a low-cholesterol diet or a low-fat diet. This is a highly regimented diet where you have to do things like count the number of potato chips."

Tetrahydrobiopterin works with PAH to metabolize Phe. Recent studies show that about 30 percent to 50 percent of PKU patients are tetrahydrobiopterin-responsive. Phenoptin is a highly purified formulation of the 6R isomer of tetrahydrobiopterin.

It is a much-needed therapy, Grass said, as most patients do not fully comply with their diets.

"For some time, there's been a large need for something that lowers phenylalanine levels and allows people to relax their diet, or minimize the effects of being off diet," he said.

While Daiichi will market the product in Japan, BioMarin intends to find a partner for all other markets outside of the U.S. The company will use its new sales force acquired from Ascent Pediatrics Inc. to market Phenoptin within the U.S.

In April, BioMarin paid $175 million to acquire Ascent, the pediatric business of Phoenix-based Medicis Pharmaceutical Corp. BioMarin gained the children's asthma drug Orapred, which was launched in 2001, and a 66-person U.S. pediatric sales force through the deal. (See BioWorld Today, April 22, 2004.)

With its own sales force, BioMarin plans to launch all of its pediatric products in the U.S., including Aryplase and Phenylase, in addition to Phenoptin. Aryplase, an enzyme-replacement therapy for mucopolysaccharidosis-VI, might be the subject of a new drug application this quarter. Phenylase, which is designed to treat severe PKU, remains in preclinical testing.

Aside from Orapred, BioMarin has one other approved product, Aldurazyme, an enzyme-replacement therapy for mucopolysaccharidosis-1, which is marketed by Genzyme General, of Cambridge, Mass. The product gained approval in 2003.

The company's non-pediatric disease products include Vibrilase to treat burns and wounds, Chondroitinase for spinal cord injury and NeuroTrans for delivering proteins across the blood-brain barrier. BioMarin intends to seek partners for those products.

BioMarin's stock (NASDAQ:BMRN) stock lost 14 cents Wednesday to close at $4.51.