AVI BioPharma Inc. announced that treatment with eteplirsen met the primary efficacy endpoint in a randomized, double-blind, placebo-controlled Phase IIb study in boys with Duchenne muscular dystrophy (DMD). Eteplirsen administered once weekly at 30mg/kg over 24 weeks resulted in a statistically significant increase in novel dystrophin (22.5% dystrophin-positive fibers as a percentage of normal) compared to no increase in the placebo group.
Eteplirsen uses AVI’s novel phosphorodiamidate morpholino oligomer (PMO)-based chemistry and proprietary exon-skipping technology to skip exon 51 of the dystrophin gene. By skipping exon 51, eteplirsen may restore the gene’s ability to make a shorter, but still functional, form of dystrophin from mRNA.
In the study, a shorter duration of eteplirsen treatment, 12 weeks, did not show a significant increase in novel dystrophin (0.79% dystrophin-positive fibers as a percentage of normal; p-value NS), despite administration of the drug at a higher dose (50mg/kg once weekly). This finding suggests that a longer duration of dosing is required before meaningful levels of dystrophin are produced. There were no significant improvements in clinical outcomes in the treated groups compared to placebo. Performance on the 6-minute walk test and other outcome measures were generally stable across most of the patients, including the placebo patients, suggesting that a longer period of observation will be required to demonstrate clinical effects of eteplirsen versus a placebo control.
Eteplirsen was well tolerated at both dose levels through 24 weeks of treatment. There were no treatment-related adverse events, no serious adverse events, and no treatment discontinuations related to eteplirsen. Furthermore, no treatment related changes were detected on any safety laboratory parameters, including several biomarkers for renal function.
“We are very encouraged by the results of this first placebo-controlled study investigating exon-skipping technology in DMD,” says Chris Garabedian, President and CEO of AVI BioPharma. “Eteplirsen represents the first drug candidate for DMD to demonstrate the production of novel dystrophin in a robust and consistent manner and these study results support advancing eteplirsen into a pivotal study.”
Filed Under: Drug Discovery
