Prosensa partnered with GSK for the development of its lead compound PRO051. both parties are operating closely together to make this drug available to patients.
Prosensa’s lead compound PRO051/GSK2402968 is highly sequence-specific, i.e. no 100% full length hits elsewhere within the individual genome, decreasing the risk for off-target effects. PRO051/GSK2402968 so exclusively induces exon 51 skipping within the DMD gene, which, given the frequencies in various international DMD mutation databases, could in theory proper the reading frame in ~13% of all DMD patients, including individuals with deletions of exon 50, exon 52, exons 45-50, exons 48-50, and exons 49-50.
In vitro studies in series of cultured individual tissue affected by several pertinent deletions demonstrated that PRO051/GSK2402968 induces exon 51 skipping independent of the type of mutation. it was also effectively tested within the hDMD mouse model expressing full length individual dystrophin. clinical proof of concept was obtained in four DMD individuals getting a single intramuscular 0.8 mg dose of PRO051/GSK2402968 [van Deutekom et al., 2007]. in this research PRO051/GSK2402968 was safe, well-tolerated, and effective in exclusively inducing exon 51 skipping and dystrophin restoration (up to 35% of normal) within the majority of muscle fibers (up to 94%) within the cured area.
In a subsequent cycle I/II dose-ranging safety study, PRO051/GSK2402968 was administered subcutaneously in the program of five weeks in 12 individuals at two European clinical centers. The research demonstrated that PRO051/GSK2402968 was well tolerated in all individuals and that novel dystrophin expression was detected in each cured patient.
An extension research is ongoing in all 12 individuals in order to collect longer term safety data before enrolling individuals for any large international multi-center pivotal research in 2010. Prosensa is also preparing for any safety and PK research in non-ambulatory DMD boys. Prosensa has partnered with GSK for the even more clinical development of PRO051/GSK2402968.
PRO051/GSK2402968 has obtained an orphan drug designation within the EU and the US.