Wednesday 17 August 2011
Next phase of Duchenne exon skipping clinical trials started
AVI Biopharma has announced that they have started the clinical trial in the US to test higher doses of the exon skipping drug eteplirsen for a longer period of time. This trial follows on from the successful trial in the UK, the results of which were published in full on 25 July 2011.
The drug being tested - now called eteplirsen - was developed by British and Australian scientists in the MDEX consortium. The Muscular Dystrophy Campaign has invested more than one million pounds into the development of this therapy over the past 20 years and was instrumental in setting up the MDEX consortium.
The previous UK trial involved 19 boys receiving weekly intravenous infusions (needle into the vein) of eteplirsen for 12 weeks at one of six different doses up to 20 mg per kg of body weight. Three of the trial participants in the higher dose groups had a strong response to the treatment in this trial, but the response was very variable from boy to boy. Read about the results of this trial.
What will happen in this trial?
In this new trial eight boys will receive the exon skipping drug for 24 weeks; half of them at a dose of 30 mg per kg of body weight and the other half at 50 mg per kg of body weight. A further four boys will receive a placebo. Neither the clinicians, participants nor their families will know who is receiving the active drug or the placebo.
Biopsies will be taken before treatment, and either at 12 weeks (30 mg per kg group) or 24 weeks (50 mg per kg group). At 12 weeks and 24 weeks all of the boys will do a six minute walk test and their muscle strength will be measured.
When will we know the results and what happens next?
The results of this trial should be available in the middle of next year. It is intended that the results will be used in the planning of a large, international phase 3 trial that is expected to start in the second half of 2012. AVI Biopharma have given assurances that the UK will be included in the phase 3 trial. It will be this trial that will give clear answers about the effectiveness of this treatment.
Dr Marita Pohlschmidt, Director of Research at the Muscular Dystrophy Campaign said:
We really welcome the start of the next phase of the clinical trial especially in preparation for a phase 3 trial that will include a larger number of boys. We are however, disappointed that the company will not continue with the trial here in the UK, because the families and the researchers in this country have invested so much time and effort and the expertise and infrastructure is already in place to continue the trial here. Given the key role the Muscular Dystrophy Campaign has played to develop this technology we don't want families in the UK feeling left behind.
Background information
So far scientists have shown this technique to be effective in a dog and a mouse model of Duchenne muscular dystrophy. These animal models have been essential for the development of the therapy prior to testing in humans.
Exon skipping is a personalised medicine - the molecular patch needs to be tailored to the specific mutation in the dystrophin gene. Mutations can occur anywhere along the gene but some areas - such as around exon 51 - more commonly have mutations than others. Although the molecular patch tested in this clinical trial can only treat 13 percent of boys with Duchenne, exon skipping has the potential to treat up to 80% of boys with Duchenne muscular dystrophy once more molecular patches are developed. More patches are already in the pipeline.
Skipping of exon 51 is also being trialled by the company Prosensa in partnership with GSK using a chemical formulation of molecular patch that differs slightly from that used by AVI Biopharma. Read about the recent Prosensa clinical trial results. A phase 3 clinical trial is now under way to test this molecular patch in more boys for a longer period of time. Please see "Further information and links" below for details of the ongoing clinical trials.
Find out how exon skipping works.
Further information and links
Read the AVI Biopharma press release.
Read about the research we're funding to develop the next generation of exon skipping drugs.
Comment or ask questions about this research in the TalkMD forum.
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Summaries of ongoing exon skipping clinical trials:
- Phase 3 study of the effect of a drug to skip exon 51 (GSK2402968)
- Testing the safety of a drug to skip exon 51 (GSK2402968) in boys who are unable to walk
- Investigating two doses of a drug to skip exon 51 (GSK2402968)
- Phase 1/2 study investigating the skipping of exon 44
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