BioMarin Initiates Phase 2 Clinical Study of 6R-BH4 in Peripheral Arterial Disease
- Category: Small Molecules
- Published on Monday, 08 January 2007 02:00
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NOVATO, CA, USA | Jan 04, 2006 | BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN) today announced that the first patient has initiated treatment in the Phase 2 clinical study of 6R-BH4 for the treatment of symptomatic peripheral arterial disease. The company expects to announce data from this study in the first half of fiscal year 2008.
"Peripheral arterial disease results from endothelial dysfunction and affects approximately eight million Americans, many of whom also suffer from intermittent claudication," stated Emil Kakkis, M.D. Ph.D., Chief Medical Officer of BioMarin. "This study is the second company-sponsored Phase 2 trial and part of a broader program to evaluate the role of 6R-BH4 in the treatment of different types of cardiovascular diseases. 6R-BH4, commonly known as tetrahydrobiopterin, is an essential enzyme cofactor that is involved in the production of nitric oxide, a molecule that has been shown in clinical studies to play a key role throughout the cardiovascular system, including regulation of endothelial function."
The Phase 2, multicenter, multinational, randomized, double-blind, placebo-controlled study is designed to compare oral 6R-BH4 to placebo in subjects with intermittent claudication (IC) caused by peripheral arterial disease. The study will be conducted at approximately 35 multinational sites and will enroll approximately 210 subjects. Among other eligibility criteria, to participate in the study, patients must have a 6-month or longer history of walking limitation due to IC, the severity of which has not changed in the past three months. Study patients will receive oral doses of 800 mg/day of 6R-BH4 or a placebo, divided into two doses for a 24-week period. The primary endpoint analysis will compare the change from baseline to Week 24 in peak walking time between the 6R-BH4 and placebo groups.
6R-BH4, commonly known as BH4 or tetrahydrobiopterin, is a naturally occurring enzyme cofactor that is required for numerous biochemical and physiologic processes, including the synthesis of nitric oxide (NO). NO has been shown to play a key protective role throughout the cardiovascular system and produces multiple positive effects, such as relaxing smooth muscle, reducing blood pressure, controlling inflammation and reducing platelet aggregation. Researchers have demonstrated that a deficiency of BH4 can disrupt NO synthesis, resulting in a loss of normal endothelial NO production. This loss of endothelial NO production, commonly referred to as endothelial dysfunction, has been associated with many cardiovascular diseases, including hypertension, diabetic vascular disease, peripheral arterial disease, coronary arterial disease and pulmonary hypertension, and has been shown to be a strong predictor of cardiovascular adverse events in a number of clinical studies.
6R-BH4 is the same enzyme cofactor currently being evaluated in BioMarin's Phenoptin(TM) (sapropterin dihydrochloride) for phenylketonuria (PKU). In March 2006, BioMarin and Serono, BioMarin's corporate partner for the Phenoptin and 6R-BH4 programs, announced positive results from the Phase 3 clinical study of Phenoptin for PKU. All primary and secondary endpoints of the study were met. The type and incidence of adverse events was similar in the Phenoptin and placebo groups. Phenoptin was well tolerated and investigators reported that no serious adverse event occurred.
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio is comprised of two approved products and multiple clinical and preclinical product candidates. Approved products include Naglazyme(R) (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin, and Aldurazyme(R) (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation. Investigational product candidates include Phenoptin(TM) (sapropterin dihydrochloride), a Phase 3 product candidate for the treatment of phenylketonuria (PKU), and 6R-BH4 for cardiovascular indications, which is currently in Phase 2 clinical development for the treatment of poorly controlled hypertension. For additional information, please visit www.BMRN.com. Information on BioMarin's website is not incorporated by reference into this press release.
This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including, without limitation, statements about: the development of its product candidate 6R-BH4 for the treatment of peripheral arterial disease and poorly controlled hypertension and the expected effects of 6R-BH4 in peripheral arterial disease, poorly controlled hypertension and other indications and the expected timing of the results from the Phase 2 study in peripheral arterial disease; and the development of Phenoptin for treatment of PKU. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: the results and timing of current and planned preclinical and clinical trials related to Phenoptin and 6R-BH4; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's 2005 Annual Report on Form 10-K and the factors contained in BioMarin's reports on Forms 10-Q and 8-K. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation, to update or alter any forward-looking statements.
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