MDA Presents Updates on Duchenne Drug Development

The Muscular Dystrophy Association (MDA) has released a report on the latest findings and developments on treatments for Duchenne muscular dystrophy that combat fibrosis and heart conditions associated with the disease. The Drug Development for DMD: February 2015 Update is a way for the association to keep the MD community informed on the advancements of the fight against DMD.

First, a research team from Stanford University in California, led by Tom Rando who is funded by the MDA, discovered that DMD can cause fibrosis in aging mice that have induced DMD and developed muscle stem cells responsible for fibrosis, instead of repairing injured muscle fibers. The mice were also found to lack functional protein dystrophin, similar to DMD patients, which provokes muscle tissue degeneration.

The findings of the study, which was published last December in the journal Science Translational Medicine, support the idea that DMD treatments also combat scarring. “These studies shed new light on the cellular and molecular mechanism responsible for stem cell dysfunction in dystrophic muscle,” said the authors, “and may contribute to the development of more effective and specific therapeutic approaches for the prevention of muscle fibrosis.”

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Second, Halo Therapeutics is currently studying HT-100, a drug developed with the support of a $500,000 MDA grant to decrease fibrosis in patients with DMD. The drug is currently in Phase 1-2 of clinical development, entitled the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of HT-100 in Duchenne Muscular Dystrophy program, designed to assess the drug in DMD male patients between 6 and 20 years old.

Third, regarding heart conditions associated with DMD, a recent study conducted at three U.S. centers suggests the drug epleronone may improve the treatment of cardiomopathy, a degeneration of the heart muscle verified in Duchenne patients. The study included 42 DMD male patients older than seven years who were suspected to have cardiac abnormalities and were receiving treatment with heart medications angiotensin converting enzyme inhibitors (ACE inhibitors) or with angiotensin receptor blockers (ARBs).

A group of participants added eplerenone to their normal DMD medication, and were found one year later to have less decline in heart function. The study, authored by cardiovascular disease specialist at Ohio State University Subha Raman and colleagues, was published last December in the Lancet Neurology. Raman believes that eplerenone may be helpful to DMD patients in early stages of the disease, despite the fact that further research is needed.

Fourth, Sarepta Therapeutics is currently studying an investigational drug called SRP-4053 in four sites across Europe that addresses DMD specific mutations. The exon-skipping drug works by blocking exon 53, which is a section of the dystrophin gene, and stimulates the production of functional dystrophin protein by the muscle cells. The company has also announced the dosing of the first patients in this study.

Sarepta currently has three clinical trials open. One of them is a phase 1-2 trial of SRP-4053, in France, Italy and the UK for DMD patients between 6 to 15 years old who are able to walk and carrying mutations possibly treatable by skipping exon 53. The second is a phase 3 study of eteplirsen in the U.S. for DMD patients from 7 to 16 years old that can walk and have dystrophin mutations potentially treatable by skipping exon 51. The last one is a safety study of eteplirsen in the U.S. for patients with advanced DMD between the ages of 7 and 21 years old who are unable to walk and who have mutations potentially treatable by skipping exon 51.

Lastly, Marathon Pharmaceuticals has been granted FDA fast track designation for its corticosteroid drug deflazacort for DMD. The FDA awarded the designation to accelerate the process of review of the drug, which is already approved in other countries. The company is currently evaluating the anti-inflammatory, corticosteroid drug in a phase 1 study with DMD male patients from 4 to 16 years old, as well as in a second phase 1 study to evaluate the safety and tolerability of deflazacort for DMD male patients that were part of the pharmacokinetic study of the drug.