PRO051/GSK2402968
Prosensa’s proprietary technology platform, correcting mutated mRNA in life threatening disorders, may be applicable to a wide variety of diseases. Prosensa has achieved first clinical proof of concept in Duchenne Muscular Dystroph, and has now also initiated (pre)clinical programs for the development of antisense products for other indications including Myotonic Dystrophy and Huntington’s Disease.
| Indication | Compound | Discovery | Pre-clinical | Phase I/II | Phase III |
|---|---|---|---|---|---|
| Duchenne Muscular Dystrophy (DMD) | PRO051 |
In October 2009, Prosensa partnered with GlaxoSmithKline (GSK) for the development of its lead compound PRO051. Both parties are working closely together to make this drug available to patients.
Prosensa’s lead compound PRO051/GSK2402968 is highly sequence-specific, with no 100% full length antisense hits elsewhere in the human genome, minimizing the risk for off-target effects. PRO051/GSK2402968 specifically induces exon 51 skipping in the DMD gene, which, given the frequencies in various international DMD mutation databases, could in principle correct the reading frame in ~13% of all DMD patients, including patients with deletions of exon 50, exon 52, exons 45-50, exons 48-50, and exons 49-50.
In vitro studies in series of cultured patient cells affected by different relevant deletions demonstrated that PRO051/GSK2402968 induces exon 51 skipping independent of the type of mutation. It was also successfully tested in the hDMD mouse model expressing full length human dystrophin. Clinical proof of concept was obtained in four DMD patients receiving a single intramuscular 0.8 mg dose of PRO051/GSK2402968 [van Deutekom et al., 2007]. In this study PRO051/GSK2402968 was safe and effective in specifically inducing exon 51 skipping and dystrophin restoration (up to 35% of normal) in the majority of muscle fibers (up to 94%) in the treated area.
In a subsequent Phase I/IIa dose-ranging safety study, PRO051/GSK2402968 was administered subcutaneously during 5 weeks in 12 patients at two European clinical centers. The study demonstrated that PRO051/GSK2402968 was well tolerated in all patients and that novel dystrophin expression was detected in each treated patient. An open label extension study of this Phase I/IIa study is on-going and the 12-week data were published in NEJM in April 2011 [Goemans et al., 2011 NEJM]. Prosensa has partnered with GSK for the further clinical development of PRO051/GSK2402968.
A Phase III study (DMD114044) started early 2011 and is currently recruiting patients. Several other studies are on-going, such as a Phase II study comparing two doses (DMD114876) , a Phase II dose regimen study (DMD114117) , a safety and PK study in non-ambulatory DMD boys (DMD114118) and an open-label study
for patients that have previously participated in the 114044 or 114117 study. Details regarding the studies, such as inclusion/exclusion criteria and trial sites, are posted at the website www.clinicaltrials.gov as soon as these
are finalized and all the required approvals of authorities and ethics committees are granted. For further questions about these clinical studies the GSK call centre can be contacted at +1 877-379-3718.
PRO051/GSK2402968 has obtained an orphan drug designation in the EU and the US.