PTC Remains Committed to Ataluren for Nonsense-Mutation DMD/BMD

Update (July 25, 2012): This story was updated to reflect the fact that PTC has announced its intention to begin an open-label trial of ataluren in DMD/BMD for former ataluren trial participants in Europe, Israel and Australia.

Editor's note (Nov. 9, 2011): This story was updated to reflect the fact that, in Canada, access to ataluren for former trial participants is through a special access program, rather than an extension study.

PTC Therapeutics of Plainfield, N.J., and Genzyme of Cambridge, Mass., announced Sept, 2, 2011, that PTC has regained worldwide rights to develop its experimental drug ataluren for the treatment of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) resulting from nonsense mutations.

Diane Goetz, PTC's director of patient and professional advocacy, said PTC remains fully committed to developing ataluren for nonsense-mutation DMD and BMD, and that its restructured agreement with Genzyme does not change the opportunity for participation in an ongoing open-label safety study for those who have been in previous trials.

Nonsense mutations, also known as premature stop codon mutations, cause cells to stop synthesizing a protein before the cell has finished "reading" the genetic instructions (RNA) for the protein. Nonsense mutations are believed to cause DMD or BMD in some 5 to 15 percent of cases.

Goetz emphasized that former participants in trials of ataluren in the United States are eligible to participate in an open-label, phase 3 study of the drug at any of 14 sites around the country. For details, see Study of Ataluren for Previously Treated Patients with nmDBMD in the US, or enter NCT01247207 into the search box at ClinicalTrials.gov.  (The phase 3 study is not open to those who have not participated in previous trials of ataluren.)

Ataluren coaxes cells to ignore nonsense mutations

Ataluren, formerly known as PTC124, is designed to cause the cellular machinery to ignore nonsense mutations in the gene for the muscle protein dystrophin and synthesize functional dystrophin protein despite the presence of this type of mutation.

A complete lack of dystrophin results in DMD, while BMD results from dystrophin protein that's partially functional. Both diseases result from mutations in the dystrophin gene.

Low-dose ataluren regimen showed modest benefit

In October 2010, PTC announced that participants in a 174-person, 48-week trial of ataluren in nonsense-mutation DMD/BMD who received the lower of two dosing regimens of this oral drug showed a slower decline in walking ability than those in the high-dose or placebo groups.

The drug has not yet received approval for the treatment of any disease by any regulatory agency.

Meaning for people with nonsense-mutation DMD/BMD

Worldwide development of ataluren in nonsense-mutation DMD or BMD will continue, now under the sole purview of PTC Therapeutics.

A July 2008 agreement had awarded commercial development rights for ataluren in the United States and Canada to PTC and development rights for this drug outside the United States to Genzyme.  In April 2011, Genzyme became a wholly owned subsidiary of the multinational pharmaceutical company Sanofi-Aventis.

Those who have been receiving ataluren after having participated in an ataluren trial for DMD/BMD in the United States can continue to receive it through participation in an ongoing ataluren extension study if they wish to do so. (Extension studies are studies that follow patients who have participated in earlier clinical trials.)

Those who have participated in ataluren trials for DMD/BMD in Canada can receive the drug through a special access program. Former participants in Canada should contact the study coordinator or principal investigator at their former study site if they wish to participate in this type of program.

In November 2011, PTC notified the DMD/BMD community outside North America that it plans to initiate an open-label study of ataluren for all former participants in ataluren trials for DMD/BMD in Europe, Israel or Australia, regardless of whether or not they are still walking. PTC said former trial participants will be contacted by their principal investigator or a member of his or her staff when enrollment begins.

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