Assistant Managing Editor

BioMarin Pharmaceutical Inc. launched a pivotal Phase III trial of enzyme replacement therapy (ERT) GALNS (N-acetylgalactosamine 6-sulfatase), the drug widely considered to be a key growth driver for the Novato, Calif.-based biotech.

The study is slated to enroll about 160 patients with mucopolysaccharidosis Type IVA, a lysosomal storage disorder also known as Morquio A syndrome that's characterized by excessive storage of karatan sulfate and can lead to systemic skeletal dysplasia, short stature and joint abnormalities. UK regulators signed off on the trial design late last month, and BioMarin recently received FDA feedback under the special protocol assessment process.

"This is a big step forward," company spokesman Bob Purcell told BioWorld Today. "It's a key program in a key indication and one with a huge unmet need."

No therapies currently are available for MPS IVA, a condition believed to affect between 1 in 200,000 and 1 in 250,000 live births – about 2,500 to 3,500 patients worldwide. BioMarin will test two doses of GALNS – 2 mg/kg per week and 2 mg/kg every other week – over a six-month period. The primary endpoint will be the six-minute walk test, while secondary endpoints will evaluate the three-minute stair climb test and urine keratin sulfate concentration.

The company used those same endurance endpoints in an earlier Phase I/II trial testing GALNS (also known as BMN 110). Data from that trial wowed investors last year, showing clear improvements over baseline in both the six-minute walk and three-minute stair climb. Results also showed that patients' karatan sulfate levels fell within a few weeks of starting treatment. (See BioWorld Today, Feb. 8, 2010.)

Wells Fargo Securities analyst Brian Abrahams noted that Phase III trial is powered to detect a 40-meter improvement over 24 weeks between GALNS and placebo. "Under the statistical plan, GALNS would demonstrate superiority with either arm reaching a "p" value of < 0.025 or with the combined arms showing a "p' value of < 0.05," he wrote in a research report, adding that the "trial design is in line with expectations."

BioMarin expects enrollment to take anywhere from a year to 18 months, Purcell said. Pending positive results, that would put a new drug filing in 2013.

The firm has not disclosed the cost of the GALNS study, expected to be the largest ERT pivotal trial ever conducted, but BioMarin should have enough cash on hand to get the drug through regulatory processes. As of Sept. 30, the company had about $440.9 million in cash, equivalents and long-term investments.

Analysts have predicted that GALNS could end up the star of BioMarin's ERT franchise, possibly doubling the sales of Naglazyme (galsulfase) for MPS VI, which are expected to hit $300 million at peak.

BioMarin also markets Aldurazyme (laronidase) for MPS I with partner Cambridge, Mass.-based Genzyme Corp., and investors have been anxiously following Sanofi-Aventis SA's attempted takeover of the big biotech. Should Genzyme be acquired, BioMarin essentially could name its price for Genzyme to buy or sell its interest in Aldurazyme under a change-of-control clause in the firms' collaboration.

GALNS rights are held solely by BioMarin, and it's unlikely the biotech will partner. Despite its modest size, the firm has its own overseas sales force, currently handling distribution of Naglazyme in more than 30 countries. BioMarin Europe Ltd. is based in Dublin, Ireland, with branch offices across Europe, and the firm also has BioMarin Brasil Farmaceutica to reach the Latin American markets.

Behind the GALNS program, BioMarin is "very focused" on PEG-PAL, a pegylated recombinant phenylalanine ammonia lyase set to move into a Phase IIb trial in phenylketonuria patients with severe disease, Purcell said.

Last month, the company started Phase I/II trials with BMN 701, a fusion protein of insulin-like growth factor 2 and acid alpha glucosidase, in Pompe disease and with BMN 673, a poly ADP-ribose polymerase inhibitor for genetically defined cancers. BMN 701 was acquired via an August buyout of Zystor Therapeutics Inc., while BioMarin picked up rights to BMN 673 in its acquisition of Lead Therapeutics Inc. a year ago. (See BioWorld Today, Feb. 8, 2010, and Aug. 19, 2010.)

Shares of BioMarin (NASDAQ:BMRN) closed at $25.90 Tuesday, up 48 cents.