BioMarin Pharmaceutical has announced that the first patient has initiated treatment in the Phase 2a clinical study of 6R-BH4 (sapropterin dihydrochloride) for the treatment of sickle cell disease (SCD).
The company expects to announce data from this study in the first half of 2008.
"The sickle cell disease indication fits well strategically with our focus on rare, undertreated genetic diseases. SCD is an orphan disease with 70,000 to 100,000 patients in the United States, according to the CDC. It is well- diagnosed at birth, but there is only one approved drug treatment option currently available which is used by a minority of patients due to toxicity problems," said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin. "6R-BH4 is an essential enzyme cofactor that is involved in the production of nitric oxide, a molecule that has been shown to play a role in the regulation of endothelial function. Studies of SCD patients suggest that endothelial dysfunction may play a role in sickle cell disease, and studies in an animal model of SCD suggest the potential utility of 6R-BH4 in the treatment of the vascular problems found in this disease."
The Phase 2a multi-center, open-label study is designed to assess the safety and biologic activity of escalating doses of 6R-BH4 in patients with SCD. The study will be conducted at approximately six U.S. sites and will enroll approximately 40 subjects. Among other eligibility criteria, to participate in the study, SCD patients must be at least 15 years of age and not receiving hydroxyurea therapy. Study patients will initially receive a low, once daily oral administration of 6R-BH4 (2.5 mg/kg) and will gradually escalate every four weeks to a final dose of 20 mg/kg/day during a 16-week dose-escalation phase. Patients will be monitored for physiological and biochemical markers of endothelial function. After 16 weeks, patients who show improvement in physiological or biochemical markers of endothelial function and/or derive clinical benefit from 6R-BH4 will have the option to continue drug treatment for up to two years. During this long-term treatment period, patients will also be monitored for sickle cell crises and other vasoocclusive events which are the key problems facing SCD patients.
The primary objective of this study is to evaluate the safety of oral 6R- BH4 administered in escalating doses in patients with sickle cell disease. The secondary objective is to evaluate changes in physiological and biochemical markers of endothelial function which underlie some key aspects of SCD.