BIOMARIN'S COMPOUND MISSES GOAL IN PHASE II HYPERTENSION TRIAL

BioMarin Pharmaceutical announced results from its Phase IIa, placebo-controlled, double-blind study of 6R-BH4 in patients with poorly controlled hypertension. Results demonstrate that there was no statistically significant or clinically meaningful effect of 6R-BH4 on any efficacy or safety parameter measured relative to placebo.

"We are surprised and disappointed by these results, especially considering the numerous encouraging preclinical and clinical studies of 6R-BH4 in diseases with endothelial dysfunction," Jean-Jacques Bienaime, CEO of BioMarin, said. "We have no immediate plans to change the course of ongoing or planned clinical studies of 6R-BH4."

The eight-week, multicenter, randomized, double-blind, placebo-controlled study enrolled 116 patients with poorly controlled systemic hypertension, approximately half of which had Type 2 diabetes. Patients also had elevated blood pressure while on at least two different medications for hypertension. Study patients received oral doses of 5 mg/kg of 6R-BH4 or placebo twice daily.

The company still plans to file a new drug application for Phenoptin for treating phenylketonuria sometime next quarter, even though 6R-BH4 is the active ingredient in Phenoptin. The compound works by an entirely different mechanism of action and metabolic pathway in phenylketonuria than in hypertension.

The compound, 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.