There have been several developments in the past month with regard to the development of treatments for Duchenne MD. This includes two “firsts” for Duchenne MD – the first successful phase 3 clinical trial and the first New Drug Application to the US regulatory authorities (the FDA). In addition, a clinical trial of a gene therapy approach to boost muscle growth has started.

Idebenone slows respiratory decline

The results of a phase 3 clinical trial of idebenone (also known as Raxone or Catena) were published in the journal The Lancet on 2 May 2015. Swiss pharmaceutical company Santhera conducted the trial which involved 64 boys with Duchenne MD between the ages of 10 and 18.  Most of the participants were wheelchair users.

The results showed that idebenone was able to significantly slow the decline in breathing ability. Peak expiratory flow – the ability to breathe out – was measured using a peak flow meter, a small, hand-held device. Over the course of the one-year study the peak expiratory flow of those taking idebenone declined by three percent on average, compared with nine percent decline in those taking a placebo. In addition, the number of patients reporting upper respiratory tract infections was lower in the idebenone group. Strikingly, 45 percent of the boys on idebenone had no decline in peak expiratory flow over the course of the study, compared to 24 percent of those on placebo. These results have led to the study being hailed “the first ever successful phase 3 trial in DMD.”

Importantly, treatment with idebenone was safe and well tolerated. The only side-effect, experienced by some of the boys, was transient and mild diarrhoea, a known side effect of idebenone. Additional analysis of the results from the trial showed that boys under the age of 14 had a slightly better response to treatment, indicating that early treatment might be beneficial.

The positive results of this trial are good news because respiratory failure is a major problem for boys and young men with Duchenne MD as they get older; leading to reliance on ventilators and shortened life expectancy. Currently the only treatment known to delay the onset of respiratory problems is corticosteroids, but not everybody with Duchenne MD responds to steroids to the same extent and often the side-effects are intolerable, so idebenone may offer an alternative. Although patients taking steroids were not included in this trial, it is thought that idebenone may also benefit them and it could be taken at the same time.

Santhera is engaging in talks with drug regulators regarding the licensing of this medicine and applications for its regulatory approval are anticipated in the near future.

BioMarin takes drisapersen forward

In November last year US pharmaceutical company BioMarin bought Dutch biotech company Prosensa and has taken over development of their panel of exon skipping drugs. This includes the most advanced drug drisapersen which is designed to skip exon 51 in the dystrophin gene, which has the potential to treat approximately 13 percent of boys with Duchenne MD.

It was announced on 27 April 2015 that BioMarin had completed the application to the Food and Drug Administration (FDA) in the US for regulatory approval of drisapersen. This is the first submission to the FDA for a DMD drug. Prosensa started the FDA submission process in October. BioMarin also intends to submit an application to the European Medicines Agency in mid 2015. A separate application will be required to the Australian Therapeutic Drugs Administration before drisapersen would become available here.

On 14 April 2015 BioMarin announced that all boys with Duchenne MD who previously participated in the Prosensa drisapersen trials will have the opportunity to enroll in an extension trial and receive more doses of the drug. This includes two trial sites in Australia – Sydney and Melbourne. Prosensa started the redosing program in September last year in the US and was gradually rolling out the program to European countries.

Follistatin gene therapy trial starts

Another strategy for the development of a treatment for MD is to boost muscle growth. One way to do this is to interfere with the mechanisms naturally present in the muscle that put the “brakes” on muscle growth so that muscles remain within the normal size range. The “brakes” are a protein called myostatin and blocking this protein could result in increased muscle growth and strength.

Researchers in the USA are aiming to inhibit myostatin using a form of gene therapy. It involves increasing levels of a protein called follistatin which is a natural inhibitor of myostatin. A harmless virus is used to deliver the follistatin gene inside muscle cells and these instructions are used to make the follistatin protein.

The results of a phase 1 trial of this gene therapy involving six Becker MD patients were published in January and on the back of these positive results, funding was secured to start another trial in boys with Duchenne MD. On April 9 it was announced that the first boy with Duchenne MD received the gene therapy. The trial will involve 6 boys who will receive the gene therapy by intramuscular injection.

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Uploaded 5 May 2015