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Christmas came a few days early for people suffering from phenylketonuria, as BioMarin Pharmaceutical Inc.'s Kuvan gained marketing approval as the first specific therapy for PKU, an orphan disease characterized by neural complications caused by abnormally high levels of phenylalanine in the blood and brain.

It's "very exciting news for the PKU community and everyone at BioMarin," CEO Jean-Jacques Bienaime said of Kuvan's approval, which came a day before the Dec. 14 PDUFA date, and sent the company's shares (NASDAQ:BMRN) up $1.58 to close at $29.76 Thursday, though after-hours activity showed the stock trading upwards of $34 per share.

The Novato, Calif.-based firm will waste no time getting the drug to patients, with shipments to the distribution channel scheduled to begin today.

"Everything is in place and we are on track for immediate launch," Bienaime told investors in a conference call, adding that the small sales force is ready to go and sufficient amounts of the product have completed manufacturing. Kuvan is approved as an orphan drug, which guarantees it seven years of marketing exclusivity in the U.S.

The list price for Kuvan is 29 cents per mg, which BioMarin estimates will result in an average annual cost of $57,000 per patient based on an average patient weight of 45 kg, which Bienaime said is "consistent with other drugs that address significant unmet medical needs."

The company projects 2008 Kuvan sales to fall within the range of $35 million to $70 million. Bienaime attributed that broad range to unknowns regarding patient weight/dose relationship and patient response, as well as the usual uncertainties associated with "the first year of [new] product sales," and said the firm will attempt to narrow that gap as marketing progresses.

About 50,000 people worldwide are believed to suffer from PKU. Those patients lack the enzyme phenylalanine hydroxylase, which is needed to metabolize the amino acid phenylalanine (Phe), and long-term elevated Phe levels can result in severe mental retardation and brain damage, mental illness, seizures, tremors and cognitive problems. Until now, most patients have only been able to manage their disease by following a high-restrictive diet of low Phe foods.

Kuvan (sapropterin dihydrochloride) tablets is designed to reduce blood Phe levels in patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4)-responsive PKU. Its active ingredient is the synthetic form of 6R-BH4), a naturally occurring enzyme cofactor that works to metabolize Phe. Phase III trial data, including in BioMarin's May new drug application, showed that patients receiving doses of 10 mg/kg demonstrated a 29 percent mean decrease in blood Phe level compared to placebo. (See BioWorld Today, March 17, 2006.)

The drug is designed to be used in conjunction with a Phe diet, and new patients are recommended to start with 10 mg/kg doses of Kuvan once-daily for up to a month. Those who have no response at that dose level may receive increased doses of up to 20 mg/kg once-daily for up to another month. Patients who respond to Kuvan may have their doses adjusted within a range of 5 mg/kg to 20 mg/kg per day, based on a physician's evaluation.

On a post-marketing basis, BioMarin has agreed to continue a two-year extension study for pivotal patients, expected to end in mid-2008 in the U.S., as well as a single-dose QT cardiovascular study in healthy volunteers and a seven-year open-label trial in about 50 pediatric PKU patients ages eight and younger. The company also will maintain a PKU registry program.

Kuvan is partnered in Europe with Geneva-based Merck Serono SA, which submitted a marketing authorization application to European regulators in November. If approved in Europe with orphan drug status, Kuvan will be guaranteed 10 years of marketing exclusivity overseas.

Upon the MAA submission, Merck owes BioMarin a $50 million milestone payment under the companies' 2005 agreement. BioMarin anticipates that payment to be included in its fourth-quarter revenues.

Kuvan is the third BioMarin product to gain approval. The company currently markets Naglazyme (galsulfase) for mucopolysaccharidosis VI (MPS VI), and Aldurazyme (laronidase), indicated for MPS I, is marketed by partner Cambridge, Mass.-based Genzyme Corp.