Orphan Drug, Kuvan

Phenylketonuria (PKU) can be a devastating disease if left untreated. It is an autosomal recessive genetic disorder. That is to say, both parents must be carriers for the disease and pass on the trait to their child. There are treatment centers where screening for PKU can be performed to assess the risk of parents having a child with PKU. The problem with the disease occurs due to the absence of phenylalanine hydroxylase (PAH). PAH is an enzyme that normally breaks down phenylalanine (Phe) to tyrosine. Without this enzyme phenylalanine builds up in the body and can lead to serious neurological complications. The degree of PAH deficiency varies and the clinical presentation of the disease may not be the same for everyone.

Patients with PKU need to be kept on a strict diet. Foods high in protein such as meat, fish, milk, eggs and cheese are removed from the diet completely in the most severe cases. For infants, a special PKU dietary formula (e.g. Lofenalac) is available as well. Monitoring protein levels in the diets of patients with PKU is important to their overall well-being. For reasons that are not understood, the buildup of phenylalanine has adverse effects on the central nervous system.

PKU doesn't affect everyone the same since phenylalanine levels may range from a complete to partial deficiency. Poorly followed dietary regimes may lead to mental retardation, seizures, behavioral abnormalities and other neurological problems in children and infants with a complete deficiency. In the earlier years of PKU, patients were removed from their diet plans around the ages of 6-10 years. Unfortunately, several problems manifested such as a decline in IQs, learning problems, hyperactivity, eczema and personality disorders (e.g. schizophrenia). The subsequent development of problems led to the current practice of maintaining a unique PKU diet designed for each patient and the monitoring of Phe blood levels.

Until recently, monitoring the protein intake of patients with PAH deficiency has been the only way to treat Phenylketonuria. However, a new drug has been approved by the FDA on December 13, 2007 called Kuvan. This drug is being marketed by Biomarin in conjunction with Merck Serono. The drug was granted an orphan designation which means that it is indicated to treat a disease that affects less than 200,000 people. PKU fits this criterion because one out of every 12,000 - 15,000 live births in the United States is affected by this disease.

Kuvan, formerly known as Phenoptin, contains the active ingredient sapropterin dihydrochloride which is a synthetic form of the cofactor, 6R-BH4. The cofactor assists PAH in the breakdown of phenylalanine into tyrosine. Although, the drug works to decrease the level of Phe in the body it is not meant to replace PKU's dietary restrictions. Kuvan helps to maintain normal levels of phenylalanine in the blood which ranges from 2 - 6 mg/dl.

Many people are living normal lives with PKU in the United States by following their diet and checking phenylalanine blood levels frequently. Since Kuvan has only been recently approved, Biomarin has agreed to create a registry where patients taking the drug will be entered. This will allow the FDA and physicians to track Kuvan's efficacy, safety and side effects.

Sources: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01761.html, http://www.pkunews.org/about/intro.htm, http://www.biomarinpharm.com/pipeline-clinical-kuvan.shtml