* 30mg dose raises dystrophin 22.5 pct in 24 weeks
* No improvement seen in clinical outcomes
By Deena Beasley
April 2 A small trial of U.S.-based AVI
BioPharma Inc's experimental muscular dystrophy drug
met its goal of increasing levels of a key protein, but did not
demonstrate that the drug had an impact on walking ability or
other clinical endpoints.
The mid-stage trial, or Phase IIb, which involved 12 boys
with Duchenne muscular dystrophy, found that the four patients
treated for 24 weeks with a 30 mg dose of the drug, eteplirsen,
had a 22.5 percent average increase in levels of dystrophin, a
protein essential to building muscle, compared to no increase
for four patients treated with a placebo.
Duchenne muscular dystrophy -- a muscle degeneration disease
affecting young children, almost exclusively boys -- leads to
paralysis and death in young adulthood. At least 250,000 people
worldwide are believed to be afflicted with the disease.
Eteplirsen is designed to silence a specific strand of RNA
so that the body can produce the dystrophin that people with
Duchenne muscular dystrophy are unable to produce.
The trial found that the four patients treated for 12 weeks
with a 50 mg dose of the drug did not show a significant
increase in dystrophin, suggesting that a longer duration of
dosing is needed.
It also found no significant improvements in clinical
outcomes, including a six-minute walk test, in the treated
groups compared to placebo.
"We anticipate that these levels of dystrophin could lead to
significant clinical benefit if maintained over a longer course
of treatment," Dr. Jerry Mendell, director of the Centers for
Gene Therapy and Muscular Dystrophy at Nationwide Children's
Hospital in Columbus, Ohio and the study's lead investigator,
said in a statement.
There were no treatment-related adverse events, no serious
side effects, and no evidence of kidney toxicity.
AVI BioPharma Chief Executive Officer Chris Garabedian said
the company plans to discuss with U.S. regulators how best to
conduct a longer pivotal trial of the drug.
"The hope is that if we can delay or halt the progression of
the disease we would be able to avoid these kids ending up in a
wheelchair," he said. "It would avoid the need for ventilators,
maybe even prevent death."
Eteplirsen is designed to skip a specific "exon," or
protein-coding sequence of the dystrophin gene that is mutated
in about 15 percent of people with Duchenne muscular dystrophy.
AVI BioPharma is also developing drugs targeting other exon
mutations responsible for muscular dystrophy.
Garabedian said he would prefer raising funding for a
pivotal trial from capital markets, rather than a partnership.
"In the rare disease area, it doesn't take a large
commercial infrastructure to do this," he said.