The new results show that, at higher doses, AVI4658 can result in substantial production of the needed dystrophin protein in muscle fibers.
The company has not yet released results of any tests of muscle function in the 19 children in this trial.
AVI4658 is an antisense oligonucleotide that sticks to genetic instructions at a predetermined location, blocking the instructions and causing muscle cells to ignore (skip) them. AVI4658 is designed to correct DMD caused by mutations in the dystrophin gene in or near a section called exon 51. (Lack of dystrophin is the underlying cause of this X-chromosome-linked genetic muscle disease.)
The new information supplements preliminary data presented in April 2010 at the American Academy of Neurology meeting in Toronto. At that time, the company reported that the drug appeared safe and resulted in production of dystrophin in some participants in this trial. (See More Good News About Exon Skipping.)
About the new findings
On June 2, 2010, the company announced muscle biopsy sample results from the 19 participants in the phase 1b/2 clinical trial, which was conducted at two centers in the United Kingdom. The trial participants were boys with DMD ages 5-15 with mutations in the area of exon 51.
The announcement included biopsy results on participants who completed 12 weekly intravenous infusions of AVI4658 at one of six different doses (0.5, 1, 2, 4, 10 or 20 milligrams per kilogram of body weight).
In summary, here's what AVI found:
Meaning for people with DMD
This and other exon skipping trial results (see Progress in Exon Skipping for DMD) bode well for this strategy in DMD in children and young adults whose disease results from mutations in the area of exon 51 of the dystrophin gene.
AVI BioPharma plans to open a U.S. trial as soon as regulatory hurdles have been cleared. The first trial site is slated to be Nationwide Children's Hospital in Columbus, Ohio.
More information, including questions and answers about AVI4658 and an archived conference call that took place June 2, 2010, can be found on the AVI BioPharma website.