BioMarin’s Phase II arterial disease trial fails endpoint

BioMarin Pharmaceutical has announced results from its Phase II multi-center, randomized, double-blind, placebo-controlled clinical study of 6R-BH4 in patients with symptomatic peripheral arterial disease. There was no statistical significance observed between the 6R-BH4 treatment and placebo groups.

The primary endpoint of the study, peak walking time (PWT), did not show a significant difference between 6R-BH4 and placebo, and the secondary endpoint, claudication onset time, also did not show a difference. Addition of vitamin C to 6R-BH4 did not improve efficacy on PWT.

Endothelial dysfunction evaluated by peripheral arterial tonometry in a subset of patients did not show a significant benefit with 6R-BH4. Urinary protein excretion did not decrease with 6R-BH4 treatment, though there may have been some effect in the subset of patients with microalbuminuria at baseline. 6R-BH4 was well-tolerated in peripheral arterial disease patients and had a safety profile similar to previous studies, the company said.

The Phase II multi-center, randomized, double-blind, placebo-controlled study enrolled 190 subjects and was conducted at 31 sites in the US and Argentina. Approximately 161 patients completed the study. Study patients in the treatment group received a total of 400mg/day of 6R-BH4 twice per day.

Emil Kakkis, chief medical officer of BioMarin stated, We are disappointed that the results of 6R-BH4 in peripheral arterial disease were not statistically significant.

We have upcoming data in several BioMarin and investigator-sponsored studies of 6R-BH4 including proteinuria, pulmonary arterial hypertension and 6R-BH4 plus vitamin C in patients with endothelial dysfunction. Along with the prior results in sickle cell disease, these data will determine the future of the 6R-BH4 cardiovascular program once all the studies are complete.