MERCK SERONO REPORTS RESULTS FROM PHENYLKETONURIA STUDY

Merck Serono announced positive results from a Phase III study of Phenoptin (sapropterin dihydrochloride), in combination with diet, in patients 4 to 12 years old. Phenoptin is an investigational oral small molecule, being developed in partnership with BioMarin, for the treatment of patients with phenylketonuria (PKU) who have elevated phenylalanine (Phe) levels.

The 11-week, multicenter, double-blind, placebo-controlled, Phase III study enrolled 90 patients with blood Phe levels below 480 micromoles/L. Patients were screened for responsiveness to Phenoptin with an open-label, one-week treatment at a dose of 20 mg/kg/day. Of the 89 patients who completed Part 1, 50 subjects demonstrated a blood Phe reduction of at least 30 percent, and 45 were randomized to Phenoptin (20 mg/kg/day) or placebo in a 3-1 ratio and enrolled in the 10-week, double-blind, placebo-controlled portion of the study. For the first three weeks, patients maintained their pre-existing restricted diet with no supplementation of phenylalanine. Thereafter, every other week, specific amounts of phenylalanine were added (or removed) to the restricted diet of each patient according to pre-defined blood phenylalanine levels. The maximum amount of Phe that could be added to a patient diet during the study was 50 mg/kg/day.

The results show that all prespecified efficacy and safety endpoints of the double-blind, placebo-controlled study were met. Phenoptin treatment caused a significant increase in phenylalanine tolerance as well as a reduction in blood phenylalanine levels. In addition, the data showed that Phenoptin was well tolerated in younger PKU patients who were under dietary control.

In the primary endpoint, Phenoptin enabled a mean increase of 20.9 mg/kg/day in Phe supplementation for those patients on Phenoptin. Patients treated with Phenoptin were able to, on average, double their baseline intake. At week 10, they were able to take a mean total Phe intake of approximately 43.8 mg/kg/day, while maintaining controlled blood Phe levels. The mean Phe tolerance represents approximately half the amount of Phe in a normal diet.

PKU, a genetic disorder, is caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). PAH is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and brain, resulting in a variety of complications including severe mental retardation and brain damage, mental illness, seizures and tremors, and cognitive problems. Phenoptin received orphan drug designation to treat PKU from both FDA and European Medicines Agency.