Thank you Biomed for the very imformative article. Thank you Califund for data. The last two paragraphs below are right out of the BMRN website. We can trust them. Together, we know that 6R-BH4 study reported in the article has admixture of 6S form of BH4 which is undesirable. Yet, the article reports 50+% response! Can you imagine what kind of response we'll get with Phenoptin? Here are the clips. Tetrahydrobiopterin (BH4), a cofactor essential for the functioning of certain large molecules and enzymes, works with PAH to metabolize Phe. Tetrahydrobiopterin has been used to successfully treat BH4 deficiency, a rare metabolic disease also caused by high Phe levels, for approximately 20 years. Several recent studies indicate that approximately 30 to 50 percent of PKU patients are tetrahydrobiopterin-responsive. In 1999, researchers discovered that a highly purified 6R form of tetrahydrobiopterin, which contained lower levels of the 6S isomer than in prior formulations, enhanced tetrahydrobiopterin responsiveness in people with PKU. Prior to this time, tetrahydrobiopterin contained a larger fraction of the 6S isomer that has been demonstrated to inhibit Phe metabolism. Phenoptin will be a highly purified formulation of the 6R isomer of tetrahydrobiopterin.
BioMarin has a worldwide exclusive license on intellectual property relating to the synthesis, stabilization and use of 6R-BH4 for PKU and other genetic disease indications, and has right of first refusal to develop 6R-BH4 for cardiovascular and other indications. BioMarin will pay Merck Eprova a royalty, which is dependent on specified cost of goods targets, on commercial sales of Phenoptin for PKU or related indications.
The study found that 54% of patients who took their version (obtained from Schircks Lab) of 6R-BH4 had varying degrees of reduction in the blood PA level. Because there are 400 different mutations in PAH enzyme, it is not surprising that remaining 46% did not respond. BMRN's next product PHENYLASE should work for them. BH4 is only a cofactor to it.