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AVI BioPharma's eteplirsen meets primary endpoint of midstage trial in Duchenne muscular dystrophy but fails to improve clinical outcomes; shares drop

Monday, April 02 2012 | Comments
Evidence Grade 0 What's This?
Although AVI BioPharma Inc.'s eteplirsen, an investigational treatment for Duchenne muscular dystrophy (DMD) and AVI BioPharma's lead drug candidate, met the primary endpoint of a small midstage study, news that the drug failed to improve clinical outcomes sent the firm's shares down 27.9 percent.

The double-blind Phase IIb trial, known as Study 201, included 12 boys aged 7 to 13 years with DMD who had certain deletions of the dystrophin gene that made them candidates for eteplirsen therapy. The participants were randomized to receive one of two doses of eteplirsen (30 mg/kg of body weight or 50 mg/kg) or placebo, administered via once-weekly infusion. The primary efficacy endpoint was the change in the proportion of dystrophin-positive muscle fibers as measured in muscle biopsy tissue. AVI BioPharma said this endpoint was evaluated at week 12 in the eteplirsen 50 mg/kg group and at week 24 in the 30 mg/kg group.

The trial results showed that the 30 mg/kg dose level of eteplirsen was associated with a significant increase in novel dystrophin at week 24, with 22.5 percent dystrophin-positive fibers as a percentage of normal, whereas there was no increase in the placebo group. 

The data also showed that a shorter (12-week) duration of treatment did not significantly increase novel dystrophin, despite the use of a higher dose, suggesting that a longer dosing period is required for the drug to produce meaningful levels of dystrophin.

There were no significant improvements in clinical outcomes with eteplirsen as compared with placebo. The company noted that performance on the six-minute walk test, a secondary endpoint, and other outcome measures were stable among most patients, including those in the placebo group, indicating that a longer period of observation might be required to detect clinical benefits with eteplirsen as compared with placebo.

The drug was well-tolerated at both dose levels.

Eteplirsen, formerly known as AVI-4658, is designed to "skip" a specific exon of the dystrophin gene, thus restoring the gene's ability to make a shorter, but still functional, form of the dystrophin protein, according to AVI BioPharma. The Food and Drug Administration has granted the compound an orphan drug designation and fast track status in the DMD indication.

Dr. Jerry Mendell, lead investigator of the trial, said the trial results indicate that eteplirsen is producing consistent levels of the dystrophin protein, which is essential to patients with DMD, a progressive, fatal neuromuscular disorder that affects approximately one in 3,500 boys worldwide.

"We anticipate that these levels of dystrophin could lead to significant clinical benefit if maintained over a longer course of treatment," Mendell added.

Chris Garabedian, AVI BioPharma's chief executive officer, remarked that eteplirsen is the first drug candidate for DMD to demonstrate production of novel dystrophin "in a robust and consistent manner" and said the data from this study support advancing the drug into a pivotal trial.

However, an analyst cited by Reuters said investors want to know whether the drug can improve walking ability with longer-term treatment and that AVI BioPharma would need to provide additional information to ease these concerns.

The news agency noted that eteplirsen is being evaluated in an open-label extension trial, which will last for 48 weeks.

AVI shares closed at $1.11, down $0.43, in heavy trading on the Nasdaq.

This information concerns a use that has not been approved by the FDA.

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