Answers to the 'Critical Questions' About Eteplirsen for DMD

MDA asks Sarepta Therapeutics' CEO Chris Garabedian about next steps for this promising new drug for DMD

Article Highlights:
  • A part of MDA's advocacy mission is to help individuals and families get the answers they need to critical questions about drug development.  Here, Chris Garabedian, president and CEO of Sarepta Therapeutics, sorts through what’s next for the promising drug eteplirsen, as well as implications and action items for MDA families.
  • Eteplirsen — an experimental exon-skipping drug for Duchenne muscular dystrophy (DMD) that's caused by certain mutations — has shown very positive results in a 12-person phase 2b extension study.
by Annie Kennedy on January 7, 2013 - 9:11am

Quest Vol. 20, No. 1

MDA is pushing forward on all levels to accelerate the pace at which we’re able to translate scientific discoveries into improved health outcomes for individuals living with muscle disease.

Longtime members of our MDA community likely have noticed that research updates and clinical trial announcements are coming with increasing frequency and from every direction: email, Twitter, Facebook and print. But in spite of this increase in exciting research, many critical questions remain unchanged for individuals and families: What does this really mean for me or my loved one? How far off is this “promising” development from being a “real drug”? How do we distinguish one trial from another? Does this finding apply to our specific genetic mutation?

Those very questions likely are being asked right now by families affected by Duchenne muscular dystrophy (DMD) about eteplirsen, Sarepta Therapeutics’ experimental exon-skipping drug for DMD caused by certain mutations. The drug has shown very positive results in a 12-person phase 2b extension study. All trial participants showed significant increases in dystrophin production, and those who received eteplirsen at the higher dosage level for 48 weeks were able to increase compared to the beginning of the study, while those in the placebo/delayed treatment group showed a decrease in walking distance. In December, Sarepta reported 62-week results that showed benefit not only for those who received the drug all 62 weeks, but also for those who received a placebo the first 24 weeks, followed by eteplirsen. 

For answers to the critical questions that are so important to our community, we went directly to the source — the sponsors of the clinical trials. Recently, Chris Garabedian, president and CEO of Sarepta Therapeutics, helped us sort through what’s next for eteplirsen, as well as what the implications and action items are for our MDA families. In the coming months, watch for similar chats with other pharma partners regarding the many exciting trials currently in the pipeline for our neuromuscular community.

Q: We understand that your next step is a meeting with the U.S. Food and Drug Administration (FDA). When do you expect that to take place? What will occur at that meeting?

A: We plan to meet with the FDA to review the data from the phase 2b study in the first quarter of 2013. Based on those discussions, we will work toward the fastest path to make eteplirsen available to patients in the future.

It is very hard to anticipate what the FDA will require for eteplirsen approval. There are a variety of registration paths available, such as accelerated approval and the traditional phase 3 study pathway. An important regulatory advance for rare diseases, PDUFA V (5), was signed into law this year. (Note: MDA was part of a coalition advocating for passage of these new regulations.) PDUFA V promotes accelerated access for patients to new therapies and accelerated development of promising therapies. There is language encouraging the FDA to use flexibility in disease areas of high unmet medical need like DMD. However, we need to meet with the FDA to understand how this language will apply in a real-world setting, such as with a drug like eteplirsen for DMD.

We plan to discuss additional clinical studies of eteplirsen with the FDA when we meet with them. The details of our trial design, including inclusion criteria, endpoints, duration, size and other aspects of the study will depend on the outcome of our discussions with the FDA.

Q: What is the difference between a phase 3 study and a “confirmatory” study?

A: The accelerated approval regulatory framework allows for the approval of an investigational drug based on a surrogate endpoint (a measure that substitutes for a true measure of disease progression) in early-phase studies if the condition is serious or life-threatening. A confirmatory study is then needed to further evaluate and confirm the efficacy and safety of a drug that is granted accelerated approval. This allows some patients to access the drug while the company continues to study the drug in a confirmatory trial in other patients. A phase 3 study is designed to further evaluate and confirm the efficacy seen in a phase 2 study. The main difference with a phase 3 study is that only patients who are enrolled in the study will be able to access the drug.

Q: Apart from FDA approval, what other hurdles must be faced before patients can obtain eteplirsen?

A: Manufacturing is an area Sarepta is devoting a significant amount of time and resources to right now. We are currently working to scale up manufacturing of eteplirsen to support future clinical devel-opment and to meet patient needs. We have a plan in place to meet this challenge, but we must be thorough and methodical to ensure we are successful.

Q: What, if anything, can the DMD community do to ensure that eteplirsen is available as soon as is safely possible?

A: As patients and caregivers, you have a powerful voice in educating the public about the disease and its impact. We would recommend that parents connect with existing organizations, such as MDA, that are supportive of the interests of all patients, and that are undertaking important initiatives to efficiently and responsibly meet patient needs.

Q: What is your plan to address other deletions with your exon-skipping technology?

A: Our goal is to pursue exon-skipping therapeutics for all DMD patients who can benefit from our technology, including those with rare deletions. We are actively conducting research on additional exon-skipping compounds that target exon 45, exon 50 and exon 53. We are in the process of establishing additional partnerships and collaborations to address other exons and to move the entire platform forward.

Q: If a phase 3 trial is required, how would an individual patient go about trying to be a part of that trial?

A: We will keep the patient community informed through organizations such as MDA as we make progress on the design and planning of any additional clinical studies. We also will have updates on our website and To receive Sarepta updates via email, please send an email to and ask to be included on our distribution list.

For more, read What’s Next for Eteplirsen? Sarepta Discusses FDA Approval and Future Trials.

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