making muscle wasting history

Forty-Eight Week Follow-Up Data from a Phase I/IIa Extension Study of PRO051/GSK2402968 in Subjects with Duchenne Muscular Dystrophy

The following Phase I/IIa extension study results were presented at the AAN conference by Dr Goemans on 13 April 2011.

Nathalie Goemans, Leuven, Belgium, Mar Tulinius, Gothenburg, Sweden, Rosamund Wilson, Marlborough, Wiltshire, United Kingdom, Judith van Deutekom, Sjef de Kimpe, Giles Campion, Leiden, The Netherlands

OBJECTIVE: To evaluate the efficacy and safety of 48 weeks of treatment with PRO051/GSK2402968 in boys with Duchenne muscular dystrophy (DMD).

BACKGROUND: DMD patients suffer from progressive muscle degeneration due to mutations in the DMD gene and resulting absence of functional dystrophin in the muscle cell wall. PRO051/GSK2402968 is an antisense oligonucleotide compound which induces exon 51 skipping during pre-mRNA splicing and produces novel dystrophin expression in a subpopulation of DMD patients.

DESIGN/METHODS: Twelve DMD patients with mutations correctable by skipping exon 51, (11 ambulatory, 1 non-ambulatory at study entry) completed a dose-escalation Phase I/IIa study (Netherlands Trial Register #NTR124) and entered the open-label extension study. Subjects were to receive weekly subcutaneous injections of 6mg/kg of PRO051/GSK2402968 in the extension study, regardless of earlier dose. All subjects were at stable steroid doses during the study. Assessments were performed at baseline and 4-week intervals thereafter.

RESULTS: All boys reported treatment-emergent adverse events (AE). The most common AEs were increased urinary 1-microglobulin (100%), proteinuria (92%) and injection site reactions (100%). However, the majority of AEs were considered to be mild; there were no severe treatment-related AEs. There was some evidence of mild proteinuria, confirmed as greater than the upper limit of normal range (>0.15g <0.3g/24hrs), in four boys at subsequent 24-hr collection. Increases in some renal and hepatic parameters were observed but none were considered progressive. Four serious AEs (not related to treatment) were reported. There was an improvement in 6-minute walking distance test (6MWD) from 12 weeks; this was maintained until week 48, when the mean (SD) improvement in 6MWD was +29 (80)m.

CONCLUSIONS: PRO051/GSK2402968 6mg/kg administered weekly by subcutaneous injection was generally well tolerated across