Sarepta Therapeutics presented new favorable safety and efficacy results for its experimental exon-skipping drug eteplirsen, designed to treat Duchenne MD caused by specific dystrophin mutations
Update (Feb. 5, 2014): An analysis of pulmonary function tests at 120 weeks (2.3 years) found boys treated with eteplirsen showed a stabilization of respiratory function over a time period and in an age group where a decline would have been expected. Sarepta announced these results in a Feb. 5, 2014, press release.
Sarepta Therapeutics, developer of the experimental exon-skipping drug eteplirsen to treat Duchenne muscular dystrophy (DMD), has announced favorable 120-week results related to efficacy and safety from its phase 2b eteplirsen trial. The announcements were made Jan. 15, 2014, at the J.P. Morgan Healthcare Conference in San Francisco and via a Jan. 15 press release.
"We are happy to see that, after 120 days of treatment, the eteplirsen data still look strong," said Jane Larkindale, MDA's vice president of research. "The drug appears safe, and there are indications that it might be helping to stabilize walking ability in the small cohort of patients in the trial. MDA is waiting anxiously to hear what the next steps will be for this drug."
MDA has funded the development of exon skipping as a strategy to treat DMD since the 1990s. It provided supplemental funding to help defray costs for participants' travel and other expenses associated with the phase 2 trial.
The supporting materials (slides) from the J.P. Morgan conference presentation, delivered by Sarepta CEO Chris Garabedian, are available on the Sarepta website at Events & Presentations.
Highlights from the Jan. 15 presentation and press release follow.
About the phase 2b eteplirsen study
The phase 2b eteplirsen study involves weekly intravenous infusions of eteplirsen, a drug designed to coax cells to "skip" (leave out) exon 51 (section 51) of the gene for the dystrophin protein and create smaller-than-normal, but functional, dystrophin protein molecules in muscle tissue.
The study includes boys with DMD who were 7 to 13 years old at its start; have a dystrophin gene mutation potentially treatable by skipping exon 51 of the dystrophin gene; were able to walk 200 to 400 meters (656 to 1,312 feet) in six minutes at the start of the study; and were receiving treatment with a stable dose of oral corticosteroids for at least 24 weeks prior to study entry.
The main outcome measures for this study are production of new dystrophin protein — the protein that's needed but missing in DMD-affected muscles — and the distance walked in six minutes, known as the "six-minute walk test."
At the start of the trial, there were 12 boys with DMD who met the criteria. Eight were assigned to a "continuous treatment" eteplirsen group and received weekly infusions of eteplirsen at either 30 milligrams per kilogram of body weight (four boys) or 50 milligrams per kilogram of body weight (four boys). These two groups are later referred to in summaries of results as the "continuous treatment" group.
Also at the start of the trial, four participants were assigned to receive placebo infusions for the first 24 weeks, after which two were assigned to the 30 milligrams per kilogram eteplirsen group, and two were assigned to the 50 milligrams per kilogram eteplirsen group. These two groups, combined, are later referred to in summaries as the "placebo/delayed treatment" group.
Early in the study, two participants lost the ability to walk and therefore could not undergo further testing on the six-minute walk test. They did stay in the trial, however, and were evaluated on other measures. Summaries of six-minute walk test data therefore include only 10 participants.
Six-minute walk test results
New data about the distance participants could walk at the 120-week (2.3 years) point in the phase 2b study were presented yesterday (Jan. 15, 2014). The data show:
The safety and tolerability of eteplirsen appear very good so far:
Dystrophin protein production was evaluated by analysis of muscle biopsy samples taken at 12, 24 and 48 weeks (no further biopsies were done after 48 weeks):
Sarepta's DMD drug development plans
In his Jan. 15 presentation, Sarepta CEO Chris Garabedian said that the active part of the eteplirsen molecule (the chemical sequence that interacts with the dystrophin genetic instructions) and the molecule's "backbone" (based on "PMO" chemistry) are, in Sarepta's view, different from and better than those proposed for exon-skipping DMD drugs from other companies. He also said: