Drug Development for DMD: February 2015 Update

This report on treatment development for Duchenne muscular dystrophy contains news about fighting fibrosis (scarring), treating DMD-related heart disease, exon skipping and the corticosteroid deflazacort

Article Highlights:

  • A laboratory study conducted in dystrophin-deficient mice bolsters support for developing drugs that fight scar tissue formation in DMD.
  • The drug eplerenone, added to existing treatment, improved cardiac outcomes in a trial of boys with DMD.
  • Sarepta Therapeutics announced it has started dosing patients in a trial of SRP-4053, which is designed for DMD patients with mutations near exon 53 of the dystrophin gene; the trial is in Europe.
  • Marathon Pharmaceuticals is studying the potential of the corticosteroid drug deflazacort as a treatment for DMD; the drug is approved in some countries but not in the U.S.


by Margaret Wahl on February 2, 2015 - 12:04pm

Development of treatments for Duchenne muscular dystrophy (DMD) continues to advance. Many of the new investigational drugs are potentially applicable to all DMD patients, while a few target those with specific mutations in the dystrophin gene.

Fighting fibrosis

MDA grantee Tom Rando at Stanford (Calif.) University, and colleagues, recently found that aging mice with a DMD-like disorder have muscle stem cells that are on path to cause scarring (“fibrosis”), rather than repair, of damaged muscle fibers. Like patients with DMD, these mice lack the muscle protein dystrophin, causing degeneration of muscle tissue. The findings add support for developing DMD therapies that fight fibrosis.

The investigators published their results Dec. 17, 2014, in Science Translational Medicine. “These studies shed new light on the cellular and molecular mechanism responsible for stem cell dysfunction in dystrophic muscle,” they say, “and may contribute to the development of more effective and specific therapeutic approaches for the prevention of muscle fibrosis.”

In 2013, MDA awarded a grant of $500,000 to Halo Therapeutics -- now Askashi Therapeutics -- to develop HT-100, a drug designed to reduce fibrosis in DMD-affected muscle. HT-100 is now being tested in a phase 1-2 trial in boys and young men with DMD who are 6-20 years old and meet other study criteria. For details, see Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of HT-100 in Duchenne Muscular Dystrophy; or enter NCT01847573 in the search box at ClinicalTrials.gov.

Adding eplerenone may improve cardiac outcomes

The drug eplerenone, which increases water excretion, may have a role to play in treating the heart muscle degeneration (“cardiomopathy”) seen in DMD. 

Investigators at three U.S. centers studied 42 boys with DMD who were at least 7 years old with signs of cardiac damage who were being treated with the heart medications angiotensin converting enzyme inhibitors (ACE inhibitors) or with angiotensin receptor blockers (ARBs). Study participants were randomly assigned to continue receiving their current heart medications plus the drug eplerenone, or their current heart medications plus a placebo. After a year, those in the eplerenone group showed a slower decline in heart function than those who received the placebo.

Subha Raman, a cardiovascular disease specialist at Ohio State University, and colleagues, who published their results in Lancet Neurology Dec. 24, 2014, said that use of drugs like eplerenone in DMD might be worth considering early in the disease course but that further studies are needed.

Sarepta drug targeting exon 53 being tested

Sarepta Therapeutics announced in a Jan. 14, 2015, press release, that it had begun dosing trial participants with DMD and specific mutations in the dystrophin gene with its experimental drug SRP-4053. The trial is being conducted at four sites in Europe.

SRP-4053 , an “exon-skipping” drug, is designed to block (“skip”) a section of the dystrophin gene known as exon 53, thereby coaxing muscle cells to make functional dystrophin protein.

Sarepta is developing several exon-skipping drugs for DMD, of which eteplirsen, targeting dystrophin exon 51, is the furthest along in the pipeline. MDA has been funding laboratory studies of exon skipping for DMD since the 1990s. Three clinical trials of Sarepta’s DMD drugs are open. They are:

  • A phase 1-2 trial of SRP-4053 is open in France, Italy and the United Kingdom for DMD patients who are 6-15 years old, are able to walk, have mutations that can potentially be treated by skipping exon 53, and meet other criteria. See Study of SRP-4053 in DMD Patients, or enter NCT02310906 in the search boxx at ClinicalTrials.gov.
  • A phase 3 study of eteplirsen is open at sites throughout the U.S. to DMD patients who are 7-16 years old, able to walk, have dystrophin mutations that can potentially be treated by skipping exon 51, and meet other criteria. See Confirmatory Study of Eterplirsen in DMD Patients, or enter NCT02255552in the search box at ClinicalTrials.gov.
  • A safety study of eteplirsen to treat advanced DMD is open at several U.S. sites for DMD patients who are 7-21 years old, are not able to walk more than a minimal distance, have mutations that can potentially be treated by skipping exon 51, and meet other criteria. See Safety Study of Eteplirsen to Treat Advanced-Stage DMD, or enter NCT02286947 in the search box at ClinicalTrials.gov.

Marathon studying deflazacort

Marathon Pharmaceuticals announced in a Jan. 19, 2015, press release, that it has received “fast track” designation from the U.S. Food and Drug Administration (FDA) for development of the corticosteroid drug deflazacort to treat DMD. Fast track is a mechanism the FDA uses to speed up the agency’s review process. Deflazacort is an anti-inflammatory, corticosteroid drug that is approved in a few countries outside the U.S. It’s similar to prednisone, which is widely used to treat DMD, but some believe its side effects are less severe than those associated with prednisone.

A phase 1 study to determine how deflazacort is handled by the body is open at two U.S. sites in boys with DMD who are 4-16 years old and meet study criteria. For details, see A Pharmacokinetic Study of Oral Delazacort in DMD, or enter NCT02251600 in the search box at ClinicalTrials.gov.

A second phase 1 study for boys with DMD who have participated in the pharmacokinetic study of deflazacort is testing the safety and tolerability of the drug. See A Long-Term Extension Study to Evaluate the Safety and Tolerability of Deflazacort, or enter NCT02295748 in the search box at ClinicalTials.gov.


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