Date: 2014-04-24
Type of information: Initiation of preclinical development
phase: 3b
Announcement: results
Company: Merck Serono, a Merck KGaA company (Germany)
Product: Kuvan® (sapropterin dihydrochloride)
Action
mechanism: Kuvan® is the synthetic form of 6R-BH4, a naturally occurring co-factor that works in conjunction with the enzyme phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe) into tyrosine. Clinical data show that Kuvan® produces significant reductions in blood Phe concentration in a large subset of patients.
European marketing authorization was granted for Kuvan® in 2008. Kuvan® was the first, and remains the only, medication in combination with dietary modifications in Europe designed to reduce the concentration of phenylalanine in the blood and in the brain in those patients who are responsive to Kuvan® to prevent the debilitating effects of PKU.4 Kuvan® is indicated in patients of all ages with tetrahydrobiopterin (BH4) deficiency, and in those aged 4 years and above with PKU (due phenylalanine hydroxylase enzyme deficiency) who are responsive to Kuvan. Currently, there is no licensed medication in Europe for the treatment of PKU in the 0–4 years age group. Kuvan® is marketed by Merck Serono outside the USA, Canada and Japan, by BioMarin in the USA and Canada, and under the name Biopten® by Asubio Pharma in Japan. In the USA and Europe, Kuvan® received orphan drug designation.
Disease: phenylketonuria
Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases
Country: Autria, Belgium, Czech Republic, Germany, Italy, The Netherlands, Slovakia, Turkey, UK
Trial
details: SPARK (Safety Pediatric EfficAcy PhaRmacokinetic with Kuvan®) is a Phase IIIb, multicenter, open-label, randomized, controlled study designed to assess the efficacy, safety, and population pharmacokinetics of Kuvan in patients younger than 4 years old with PKU and who have been previously shown to be responsive to Kuvan in a response test. The study was conducted under a Pediatric Investigational Plan. Patients were randomized to Kuvan (10 mg/kg/day) plus a phenylalanine-restricted diet, or to a phenylalanine-restricted diet alone, for 26 weeks, and the primary endpoint of the study was to compare phenylalanine tolerance achieved in both arms after 26 weeks of treatment. Secondary study endpoints included change in levels of blood phenylalanine during the study period, change in dietary phenylalanine tolerance over time (from baseline to 26 weeks) in both groups, as well as assessment of neurodevelopmental function, growth parameters and safety. (NCT01376908)
Latest
news: * On April 24, 2014, Merck KGaA has announced that the Phase IIIb SPARK* study has met its primary endpoint. The results of the first 26 weeks of this study demonstrated that the addition of Kuvan® (sapropterin dihydrochloride) to a phenylalanine-restricted diet in children less than 4 years of age who have phenylketonuria (PKU) and have been previously shown to be responsive to Kuvan® significantly increased tolerance to phenylalanine compared with a phenylalanine-restricted diet alone. The safety profile of Kuvan® in this population was consistent with the safety profile for Kuvan® described in the European Summary of Product Characteristics. The 26-week results will be submitted for presentation at upcoming international scientific meetings and for publication in a peer-reviewed journal. SPARK was requested by the European Medicines Agency (EMA) as a post-authorization measure and demonstrates Merck’s commitment to addressing areas of high unmet medical need. The positive outcome of the study will enable the submission of a regulatory application for a label extension later this year.
