PTC Therapeutics, Inc. announced
their first quarter report this week with an update on their placebo-controlled phase 3 clinical trial with ataluren in patients with nonsense mutation Duchenne muscular dystrophy.
Phase 3 Study
In April 2013, PTC initiated the confirmatory Phase 3 ACT DMD (Ataluren Confirmatory Trial in Duchenne muscular dystrophy) evaluating ataluren as a potential treatment for patients with nmDMD. The study is expected to complete enrollment by mid-2014.
The trial is a double-blind placebo-controlled study lasting 48 weeks that will enroll 220 boys with nmDMD (ages 7 thru 16) who can walk at least 150 meters in the 6-mile walk test (6MWT) but walk at 80% or lower than predicted for their age and height. Patients will be further stratified by age (above or below 9 yrs) and walking ability (above or below 350 m in 6MWT).
The primary outcome will be the 6MWT (change from baseline) and secondary outcomes will include timed-function tests, North Star ambulatory assessment, and quality of life measures.
Earlier this year, PTC Therapeutics announced
that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) had adopted a negative opinion on the Company's marketing authorization application (MAA) for conditional approval of ataluren for the treatment of nmDMD. This decision was likely based in the results from the company’s phase 2 study that did show the drug to improve 6MWT but the improvement was not statistically significant due to high variance in the data.
In a slide presentation
for the company’s presentation at the Deutsche Bank 39th Annual Health Care Conference on May 7th,
PTC noted they intend to request a re-examination of the CHMP opinion with a final outcome expected in the second quarter of 2014, when the confirmatory study is expected to be more fully enrolled.
At the present time, it is unclear when the company will apply to the FDA for orphan drug approval.
In the Deutsche Bank Conference, Shane Kovavs, chief financial officer stated that the patient population ataluren is targeting is different patient population than the one currently being targeted by Sarepta’s eteplirsen or Prosensa’s dripersen.
Ataluren is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in non-mutation Duchenne muscular dystrophy and CFTR channel in cystic fibrosis.
About Duchenne muscular dystrophy
Duchenne muscular dystrophy is a progressive muscle disorder caused by the lack of functional dystrophin protein. Patients with Duchenne muscular dystrophy lose the ability to walk as early as age 10 and experience life-threatening lung and heart complications in their late teens and twenties. There are an estimated 35,000 patients with Duchenne in the United States and Europe, and approximately 13% are caused by nonsense mutations in the dystrophin gene.
Images obtain from PTC Therapeutics presentation