DMD/BMD: Global Trial Planned of Experimental Drug Ataluren

PTC Therapeutics CEO Stuart Peltz discusses next steps for ataluren, an experimental 'stop codon read-through' drug for Duchenne and Becker MD caused by specific mutations

PTC Therapeutics CEO Stuart Peltz
Article Highlights:
  • The experimental drug ataluren (PTC124), developed by PTC Therapeutics with support from MDA, has shown encouraging results in a phase 2b study in boys with DMD/BMD due to a premature stop codon (nonsense mutation).
  • PTC has designed a global, phase 3 confirmatory study of ataluren with the goal of full approval of the drug in both the United States and Europe; the trial is expected to open during the first quarter of 2013.
  • Participants in the phase 2b trial who received a therapeutic dose of ataluren walked approximately 30 meters (about 98 feet) farther in six minutes than did participants taking a placebo; the drug was well-tolerated.
  • “PTC’s goal is to continue these trials until ataluren is commercially available,” said PTC CEO Stuart Peltz in answering questions about ataluren’s trial results to date and plans for the phase 3 global trial going forward.
by Margaret Wahl on February 21, 2013 - 4:31pm

Trials of the experimental muscular dystrophy drug ataluren showed that the drug was generally well-tolerated and slowed the rate of decline in walking ability, compared to the placebo group.

After consulting with regulatory agencies in Europe and the United States, biopharmaceutical company PTC Therapeutics has decided to move ahead with a global, phase 3 confirmatory study of ataluren. Trial sites will be in the U.S. and at least 10 other countries.

“We have benefited from clear guidance from the regulatory agencies regarding their expectations, said Stuart Peltz, CEO of PTC Therapeutics. “The goal is full approval of ataluren in both territories based on data from this study.”

The global trial intends to enroll 220 boys with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD)  caused by a so-called nonsense mutation. Results are expected in 2015.

If your son has a nonsense mutation in the dystrophin gene, please consider participating in the phase 3 trial,” said Peltz. “PTC’s goal is to continue these trials until ataluren is commercially available.”

What is ataluren?

Originally dubbed PTC124, ataluren’s development by PTC Therapeutics of South Plainfield, N.J., was supported in part by a $1.5 million grant from MDA in 2005.

The drug is designed to cause muscle cells to "ignore" or "read through" a type of mutation known as a premature stop codon, or nonsense mutation, in the dystrophin gene.

This type of genetic flaw is the underlying cause of DMD/BMD about 10 to 15 percent of the time. It causes cells to stop synthesizing the dystrophin protein before the protein has been completed. When cells are able to "read through" a premature stop codon in the dystrophin gene, they make functional dystrophin protein.

In December 2012, the European Medicines Agency (EMA) confirmed that PTC had completed its application for conditional approval of ataluren and that the agency would begin reviewing the application. At that time, PTC also said it planned to enroll participants in a phase 3 trial of ataluren that it hoped would serve as the basis for full approval of the drug in the U.S. and the European Union (EU).

Ataluren Q&A

Below, PTC CEO Stuart Peltz responds to questions from MDA about ataluren development up to now and where it’s going in the future.

Q: What results did you see when ataluren was given to people who have Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) as a result of a premature stop codon (nonsense mutation)?

A: PTC’s phase 2b study was the first long-term, multinational, placebo-controlled clinical trial in DMD.

As part of that study, we established groundbreaking information on the natural history of DMD as well as identified what we believe to be the therapeutic dose of ataluren: 40 milligrams (mg) per kilogram (kg) of body weight daily distributed in three doses (10 mg/kg with breakfast, 10 mg/kg with lunch and 20 mg/kg with dinner).

Trial participants receiving the therapeutic dose of ataluren walked approximately 30 meters [98 feet] farther than participants on a placebo, as measured by the change in six-minute walk distance from baseline to week 48 of the study. Ataluren-treated participants also showed a slower rate of decline in ambulation than the placebo group.

Safety results in trials to date show that ataluren was generally well-tolerated. Armed with everything we have learned, we believe we have designed a confirmatory phase 3 study that will solidify what we know about the benefits of ataluren.

We know how to define a patient population for our upcoming phase 3 study so that we have the best opportunity to establish the full potential of ataluren. We also have benefited from clear guidance from the regulatory agencies regarding their expectations.

Q: When does PTC expect a decision about conditional approval of ataluren from the regulatory authorities in Europe? What will those decisions mean for the development of ataluren?

A: We expect to hear back from the European Medicines Agency (EMA) in the second half of 2013 or early 2014 regarding "conditional approval" of ataluren for DMD. The approval of ataluren would be extremely meaningful. The approval of ataluren also would mark the first therapy specifically approved for DMD, a wonderful milestone for the DMD community.

Q: What does "conditional approval" by the EMA mean? In what countries would this conditional approval apply — all the members of the European Union?

A: Conditional approval is granted based on a positive benefit-to-risk ratio in the available data. The data need not be comprehensive, but must indicate that the public health benefits of immediate availability of a medicine outweigh its risks.

The company is given obligations to fulfill, such as the conduct of further studies. The approval is renewed on a yearly basis until all obligations have been fulfilled and can then be converted from a conditional approval into a full approval.

Conditional approvals can only be granted for medicines that satisfy an unmet medical need, meaning the medicine is intended to be used for a disease or condition for which no treatment is currently available, and it is therefore important that patients have early access to the medicine concerned. Conditional approval would apply to all European Union (EU) member countries.

Q: What do you believe the EMA may ask of PTC before full approval of ataluren for DMD/BMD can be obtained? What would be the time frame for that?

A: PTC has designed a global, phase 3 confirmatory study of ataluren with input from EMA and the U.S. Food and Drug Administration (FDA). The goal is full approval in both territories based on data from this study, which will include 220 patients. We are initiating the phase 3 study and expect to have data available in 2015.

We plan to have study sites in Australia, Belgium, Canada, England, France, Germany, Israel, Italy, Spain, Sweden and the United States. Additional sites in Asia, Eastern Europe and South America also are being considered. 

Q: What, if anything, has the FDA said about approval of ataluren for DMD/BMD? What is your proposed plan to get ataluren approved in the U.S.?

A: The FDA was clear on the need for additional information to support approval. 

While we had hoped the phase 2b trial could serve as the basis for approval, we are gratified that we received specific input from the FDA in terms of its expectations, so that a positive phase 3 trial can serve as a confirmatory study and, in combination with the phase 2b study, be the basis for a New Drug Application (NDA) seeking approval in the U.S.  

Q: How long will the ataluren extension studies continue?

A: PTC is providing access to ataluren to previous trial participants in open-label studies in the U.S. and in other countries. In the U.S., additional safety data is being collected in the 106 patients currently receiving ataluren. In Canada and Europe, some of the sites have begun enrolling patients and others are in various stages of obtaining national and local regulatory permission and completing paperwork to enroll patients over the next several months. PTC’s goal is to continue these trials until ataluren is commercially available.

Q: If ataluren is conditionally approved in Europe, can people in the U.S. obtain the drug? If so, how?

A: If ataluren is conditionally approved in the European Union, it would only be available commercially in the EU. However, development in the U.S. will continue through the global phase 3 study, which we hope will serve as the basis for approval in the U.S.

Q: Do you have any information about whether production of the dystrophin protein in muscle biopsy samples correlated with muscle function?

A: We are in the process of publishing the results of the phase 2b study in a scientific journal. We are committed to sharing our data on ataluren through scientific publications and presentations so we can continue to advance not only the development of ataluren, but the knowledge of DMD drug development for the entire community.

In the phase 2a study, conducted at three clinical sites, we saw an effect on dystrophin expression that was a clear proof of concept. 

The phase 2b trial was the first long-term, multinational, placebo-controlled study that attempted to evaluate muscle biopsies for dystrophin expression with the goal of correlating protein levels with clinical efficacy outcomes. We were not able to establish this correlation in the larger study, and we believe that the available techniques for measuring dystrophin expression are not sensitive enough to establish a correlation with clinical outcomes at this time.

As agreed with regulatory authorities, we do not plan to include biopsies in the phase 3 study.

Q: What do you expect the phase 3 trial to look like, and when are they likely to be open to participants?

A: The phase 3 trial is randomized, double-blinded and placebo-controlled, meaning that participants will be assigned by chance to receive either the drug or a placebo — a substance that looks and tastes like ataluren but does not actually contain the drug — for 48 weeks. In addition to the six-minute walk test and safety, we also will be assessing secondary endpoints related to physical function and quality of life. PTC’s goal is to enroll the first patient in the first quarter of 2013.

Q: What, if anything, can the DMD/BMD community do to ensure that ataluren becomes available to patients as soon as it is safely possible?

A: If your son has a nonsense mutation in the dystrophin gene, please consider participating in the phase 3 trial. A discussion with your treating physician is a good place to start. More information about the trial will be shared through our mailing list, so please sign up at PTC Contact Us. We also will post trial information at

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