PTC Therapeutics Provides Regulatory Update on Translarna™

PTC recently participated in discussions with FDA to discuss the Refuse to File (RTF) letter issued on February 22, 2016 with respect to the company's New Drug Application (NDA) for Translarna for the treatment of Duchenne. Today PTC announced that they have recently submitted an appeal to escalate continuing discussions about the RTF decision to the next level of FDA management via the formal dispute resolution process within FDA's Center for Drug Evaluation and Research (CDER). This process exists to encourage open, prompt discussion of scientific and procedural disputes that arise during the drug development process between FDA and companies. The company has made it clear that they are willing to consider multiple paths to advance a potential FDA approval, within the dispute resolution process, including the possibility of conducting an additional clinical trial under accelerated approval.

This process, called a Formal Dispute Resolution (FDR), is a formal process that allows senior FDA officials outside of the neurology division that reviews the details of the trials to take another look at the decision.

What is the formal dispute resolution process?

The formal dispute resolution process (FDR) was created by FDA to provide a means for resolving disagreements between FDA reviewers and a company that has submitted an application for a new drug. Because a wide variety of complex and important scientific or medical issues may come up in the review process, FDA designed the FDR to allow senior FDA management to engage in an open, prompt discussion of disputes between the sponsor and the review division. There is a draft guidance document from FDA that establishes the framework for the FDR process, and which sets specific timeline goals for appeals. If sponsors are not satisfied with a decision after appeal, they may appeal again to the next level of FDA management, potentially all the way up to the Commissioner of the FDA. FDA officials have publicly suggested that the FDR process is the appropriate regulatory path for sponsors when disagreements about refusal-to-file decisions arise.

PTC’s Long History in Duchenne

Clinical trials with PTC124 (ataluren or Translarna) started in 2007. This was the first industry sponsored trial in Duchenne. There were no Duchenne-specific outcome measures and limited natural history. Clinicians in the field had NO experience with industry sponsored trials. In a manner of speaking, we were all learning to fly the plane while in the air.

Translarna is a drug for people with Duchenne who have their disorder due to a nonsense mutation or premature stop codon.

Patients and families bravely and anxiously signed up for clinical trials of Translarna. This trial was our first real hope. And it wasn’t easy. The trial started and stopped abruptly with questions around dose. The community was devastated and families watched as their sons declined. The trials restarted, two Phase 3 studies were completed, and all families continue on the extension study. To date, with few exceptions, all patients have stayed on drug, continuing Translarna for > 8 years.

Of course there are loads of opinions in the field, but the most important opinion is from those young men and their families. They do not wish to see the drug withdrawn. And they deserve this drug to be reviewed and FDA to hear their voice, learn about their experience, and understand why they continued on Translarna for all those years.

Translarna & Europe

Translarna was the first-ever drug for the underlying cause of the disease to be approved by the European Medical Agency (EMA). Translarna has been in clinical development longer than any drug for Duchenne, and now over 150 patients are receiving Translarna, some for almost a decade.

The EMA is the regulatory body for Europe that, like the FDA, reviews the results of clinical trials and determines whether a drug is approved, or licensed, so that physicians are able to prescribe it for their patients.

The company is in the midst of going through a renewal of their approval in Europe. The EMA has extended the time for the review until the end of the year. There will be no change to Translarna’s current marketing authorization status.

PTC is optimistic that Translarna will be renewed in Europe, and will continue to study Translarna in order to understand its benefits while it is making it available to patients.

Translarna was approved by the EMA after a thorough review of the results of the trials. It understands the difficulties of studying drugs for ultra-orphan diseases like Duchenne, which is even more difficult when a drug like Translarna is only for a fraction of Duchenne patients who have a nonsense mutation.

Translarna is commercially available to patients in over 20 countries, both in Europe and in other countries around the world that recognize the EMA approval.

While Translarna has been approved by the EMA and is available to people with Duchenne in many countries, it is incredibly troubling that the FDA sent PTC a refusal to file letter (or RTF). The FDA has decided not to review Translarna, robbing our families in the United States the opportunity to share their experiences with the drug. I think we all agree that we learn much more about safety and efficacy over time, outside the context of a clinical trial, in our everyday life.

Giving Translarna Equal Time

I feel strongly that FDA is wrong about not giving Translarna a full and fair review. Our young men have been in multiple clinical trials to obtain results that other regulatory bodies have used to approve the drug. 

Given FDA's recent ruling to refuse to file Translarna, I am very concerned the drug will be pulled, that is, PTC will discontinue the extension studies in the United States. There are no other drugs in the pipeline that target premature stops. None. The FDA decision not to allow PTC Therapeutics to file their data package for review and denying the company the possibility of an Advisory Committee meeting is one more blow to our community.

In fairness to the patients, there needs to be a public discussion of the data with the scientific and patient community. Even if a public hearing does not alter FDA’s eventual decision, I think that a public discussion of Translarna is necessary, fair and appropriate. FDA needs to listen to the experience of families and thoroughly evaluate the data. Our sons deserve nothing less.

Next Steps

We continue to work closely with PTC, as we have with other industry partners in the past, to determine the best path forward. PPMD will turn to this incredible community when the time is right with actions you can take to help give Translarna the opportunity for thoughtful discussion it deserves.

For now, we hope you will:

1) Join us on August 1 at 11am eastern for a webinar with PTC to discuss next steps with the FDA.

2) If you or your loved one have experience with Translarna, please fill out the Patient Experience Survey regarding Translarna so that we can continue to compile the experiences of our community with this therapy.

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