DMD: Phase 2 Trial of GSK Exon-Skipping Drug Opens in US

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Pharmaceutical company GlaxoSmithKline has announced the opening of a U.S.-based phase 2 trial of its exon-skipping drug GSK2402968, designed to treat patients with Duchenne muscular dystrophy (DMD) who have specific mutations in the dystrophin gene.

The trial is recruiting 54 boys with DMD who meet certain criteria (see below), at study sites in California, Florida, Iowa, Kansas, Maryland, Minnesota, Missouri, New York, North Carolina, Ohio, Oregon and Texas.

Favorable results reported last year

GSK2402968 is designed to change the way muscle cells interpret genetic instructions for the muscle protein dystrophin, by coaxing them to ignore ("skip") a section of the instructions known as exon 51 and piece together the surrounding instructions.

Also known as PRO051/GSK2402968, the drug is in development by the Dutch company Prosensa and by GlaxoSmithKline.

In April 2011, investigators reported that a 48-week trial of the drug in Belgium and Sweden yielded encouraging results. They saw increased presence of the dystrophin protein in muscle fibers; an increase over baseline measurements of the distance participants could walk in six minutes; and no serious adverse events.

That trial included 12 boys with DMD who received weekly injections of GSK2402968.

New study open at 14 U.S. sites

The new trial is seeking 54 boys with DMD with the following characteristics:

• at least 5 years old;

• with a dystrophin mutation potentially treatable by skipping exon 51, which includes deletions in exons 13-50, 29-50, 43-50, 45-50, 47-50, 48-50, 49-50, 50, 52 and 52-63;

• able to walk 75 meters (about 246 feet) in six minutes;

• able to rise from the floor in seven seconds or less;

• taking oral glucocorticoids (corticosteroids) for a minimum of six months prior to screening, with no significant change in daily dosage or dosing regimen for a minimum of three months prior to screening;

• without significant heart disease; and

• meeting other study criteria.

Participants will be assigned to receive one of two weekly dosage levels of GSK2402968, or a placebo.

For details and contact information, see A Clinical Study to Assess Two Doses of GSK2402968 in Subjects with Duchenne Muscular Dystrophy, or go to ClinicalTrials.gov and enter NCT01462292 in the search box.

For more information

To learn more about exon skipping in general and GSK2402968 specifically, see:

• GlaxoSmithKline Clinical Study Register — search for GSK-sponsored trials by medical condition or drug name

• Exon Skipping in DMD: What Is It and Whom Can It Help? — story explaining the science of exon skipping (Quest, Oct. 1, 2011)

• Nationwide Children's Podcast Probes Exon Skipping in DMD — a summary of, and a link to, a podcast in which molecular geneticist Stephen Wilton discusses his group's development of exon-skipping compounds to restore dystrophin production in DMD (Quest News Online, Jan. 11, 2012)

• PRO051/GSK2402968 Exon-Skipping Drug for DMD Results in Dystrophin Production, Increased Walking Distance — results of a trial of this drug conducted in Belgium and Sweden (Quest News Online, April 20, 2011)

About Clinical Trials A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur. MDA has no ability to influence who is chosen to participate in a clinical trial. To learn more, see Understanding Clinical Trials and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to ClinicalTrials.gov.