Companies Expand Development of Exon Skipping for DMD

Two pharmaceutical companies recently announced they are expanding their development and testing of exon-skipping drugs for Duchenne muscular dystrophy (DMD).

Exon skipping is an experimental strategy in which cells are coaxed to ignore ("skip") certain regions ("exons") of genetic code so that a functional muscle protein can be made despite the presence of a genetic mutation. In DMD, the goal is production of functional dystrophin protein.

AVI BioPharma targeting exons 45, 50, 51

AVI BioPharma, a Bothell, Wash., biopharmaceutical company, announced Nov. 15, 2011, that it is increasing the number of exon-skipping drugs it is developing to treat DMD in people with specific mutations in the dystrophin gene.

The company said it will enter into collaborations with Children's National Medical Center in Washington, D.C., Carolinas Medical Center in Charlotte, N.C., and the U.S. National Institutes of Health (NIH) to develop two new exon-skipping compounds — one to encourage cells to skip exon 45 and the other to skip exon 50 of the dystrophin gene. (See the Nov. 15, 2011, press release from AVI.)

AVI currently is testing its experimental drug eteplirsen, designed to cause skipping of exon 51 of the dystrophin gene. A phase 2 trial of eteplirsen in DMD is ongoing at Nationwide Children's Hospital in Columbus, Ohio, with supplemental support from MDA. This trial is no longer recruiting participants.

Results from a trial of eteplirsen in the United Kingdom, announced in July 2011, showed the drug can increase dystrophin production in boys with specific genetic mutations.

GlaxoSmithKline expanding testing of drug targeting exon 51

Multinational pharmaceutical company GlaxoSmithKline is testing GSK2402968, which targets exon 51 of the dystrophin gene, in boys with DMD with specific dystrophin mutations.

A phase 1 trial of GSK2402968 in nonwalking boys with DMD at Nationwide Children's Hospital in Columbus, Ohio, and in France, has completed enrollment, as has a phase 2 study of this drug in several countries outside the United States. A phase 3 study of GSK2402968 outside the United States remains open.

A phase 2 trial testing two doses of GSK2402968 in walking boys with DMD is now open in Cincinnati and is expected to open at  13 additional U.S. sites within the next two to three months. Participants must have specific dystrophin mutations, be at least 5 years old and meet other study criteria. (Access this trial by entering NCT01462292 in the search box at ClinicalTrials.gov.)

A new trial of GSK2402968 in nonwalking boys with DMD who meet study criteria is slated to open at one or more U.S. centers in mid-2012. The company plans to post details on ClinicalTrials.gov when they're available.

Editor's note 11/22/11: This story was edited to reflect the fact that the trial of GSK2402968 in walking boys with DMD is expected to open at 14 U.S. sites, including Cincinnati, within the next two to three months.

Two pharmaceutical companies recently announced they are expanding their development and testing of exon-skipping drugs for DMD.
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