making muscle wasting history

Initial results from systemic treatment with AVI-4658 positive

Positive RNA and Protein Signals in first cohorts (groups) analysed

• Article Posted: 06 January 2010
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AVI BioPharma has announced its initial findings from the current systemic trial of AVI-4658, its RNA-based drug designed to skip exon 51 in Duchenne patients. Action Duchenne is delighted to report that the findings are positive. Results from boys in the first four of six cohorts (groups) completed a 12 week series of treatments have now been analysed. The boys were treated with different doses of AVI 4658 (0.5, 1.0, 2.0, or 4.0mg/kg) and have had their muscles biopsied. Analysis has shown that boys receiving the 2.0mg/kg and 4.0mg/kg doses showed accurate skipping of exon 51, and one boy showed robust expression of dystrophin protein.

Professor Francesco Muntoni, Professor of Pediatric Neurology and Head of the Dubowitz Neuromuscular Centre at the UCL Institute of Child Health, London, and the trial lead investigator stated; “I am very encouraged by the evidence of accurate skipping of exon 51 in three treated patients. These results suggest that we are on the right path towards developing a drug that could play a role in the treatment of DMD. The fact that one patient at the 2.0mg/kg dose showed significant expression of dystrophin protein leads us to expect greater levels of dystrophin expression following treatment with the higher doses of 10.0mg/kg and 20.0mg/kg of AVI-4658, which are currently underway in the trial.”

The trial is to assess the safety, tolerability, pharmacokinetics (the characteristic interactions of the drug and the body in terms of its absorption, distribution, metabolism, and excretion) and efficacy of the drug, AVI-4658. It was tested on ambulatory boys (ie. those that can walk) between the ages of 5 and 15 that have an error in the gene coding for dsytrophin that could be treated by skipping exon 51. Patients were dosed once a week for 12 weeks by intravenous infusion (ie.via a vein). Nineteen patients have been enrolled and have been assigned to one of six dose cohorts. After the completion of dosing, the boys are studied for a further 14 weeks to assess the safety of AVI-4658 over the 26 week period.

Stephen B Shrewsbury, M.D., Senior Vice President and Chief Medical Officer at AVI said; “AVI-4658 continues to demonstrate the good safety profile associated with PMO-based drug candidates. Data from the recently completed series of preclinical studies required to open an IND (Investigational New Drug) in the US suggest that this good tolerability is likely to continue at higher doses. This is critically important given that any DMD drug based on exon skipping is expected to be administered regularly over the entire course of a patient’s life.”

Nick Catlin, CEO of Action Duchenne said, “This latest news from AVI BioPharma is great for those living with Duchenne, and indicates that we are getting closer to an effective treatment for this heart-breaking and severe disease. Action Duchenne is delighted and proud to be working with AVI in these very exciting times. However, we must not assume that the job is done, there is still a lot of work to do if these drugs are to provide an effective treatment for Duchenne. We need to continue our fundraising work to ensure that these drugs are brought to market as quickly, effectively and as safely as possible.”

A full version of the announcement made by AVI BioPharma is available at: http://www.avibio.com/news_detail.php?newsId=0068

http://www.avibio.com/news_detail.php?newsid=0068