Coming Full Circle: The Ataluren Ad Comm

Like any of you who participated in today’s Advisory Committee Meeting at the FDA for PTC Therapeutic’s ataluren, I am emotionally exhausted. Whether you participated by speaking during the Open Public Hearing, attending the Ad Comm on the FDA campus, submitting your written testimony, or streaming the meeting from home – I would imagine that you, too, are drained from the hours of robust discussion.

We are starting to become pros at this, the Duchenne community. And if you were part of another rare disease community, you may be envious that we continue to get these opportunities in front of regulators to share our stories. But that doesn’t make it any easier. So much rides on each of these meetings, so many lives affected.

Today was important for the entire community. Whether or not you or your child has a nonsense mutation, we all want a victory for our families. Today, we did not learn of a final outcome. That decision likely won’t come until on or about PTC’s PDUFA date of October 24, 2017. Today was another critical layer in the product review process. Today was the opportunity for three dimensions of the product experience to be explored: the applicant’s analysis (PTC), the regulator’s review of the data (FDA), and the patient community’s experience with the product (our community’s lived experience on ataluren).

Today’s process was critical and was exactly what PPMD and our community have fought to be included in for decades. Today was the day that the data is provided in context. In the context of Duchenne. Even though we may feel worn down by today, we need to recharge our batteries and, like always, continue to fight for the approval of therapies we believe so that every single person in our community has a potential treatment for Duchenne.

Thank you to the families that participated in today’s meeting. Your testimony, as well as the written testimonies of those families who submitted prior to the Ad Comm, had a tremendous effect as indicated by almost every committee member.

Ataluren Ad Comm Discussion & Voting Results

Today’s final discussion and vote are similar to scenarios we discussed in a prior webinar. The question was included in briefing documents the FDA published Tuesday. Only one question was presented with a discussion followed by a vote on that discussion. The framing of the question allowed for the Advisory Committee to indicate whether the data presented were adequate enough to be conclusive of efficacy, or whether additional studies were needed to in order to be conclusive.

The question, as well as the votes, were designed to facilitate discussion around the findings and complexities of each of the studies that had been presented throughout the day, and to potentially map out a path forward.

It is important to remember that the result of these votes do not reflect the final decision of the FDA. Discussions from today’s Advisory Committee Meeting are used to help further inform regulators before a decision is made, on or prior to the PDUFA date of October 24, 2017.

Questions from Advisory Committee following Open Public Hearing (OPH) – prior to voting: 

  • Is there documentation of the drug hiatus to support the compelling testimony brought forward by the community?
  • Longitudinal long-term follow up. How are you following over long term?
    • Best long-term data is study 019. Exposure of 3.5 years with Natural Hx comparison
  • It sounded like the longer term effect of the drug was what was most effective – and that participants transitioned from one study to another… was data collected as to the long-term impact of drug exposure?
    • FDA cautioned that Long-term pulmonary data has not been provided to the FDA for analysis.
    • There is no way for FDA to adjust P value for multiple doses and multiple endpoints
  • Request for description of Study 2021
    • This is a 71 week placebo controlled double blinded study as a PTC’s part of post-market commitment to the EU

Question posed by FDA for the Advisory Committee:

1. VOTE:
The best interpretation of the information presented today regarding the use of ataluren for the treatment of dystrophinopathies resulting from nonsense mutations in the dystrophin gene is that:

  • a. The data suggest that ataluren is not effective – 0 votes
  • b. Although it is possible that ataluren may be effective, the data are inconclusive, and more work would be needed to establish whether ataluren is effective – 10 votes
  • c. The data are sufficient to conclude that ataluren is effective – 1 vote (Jeff Watkins)

Question clarified that OPH testimony as to be included in the ‘totality of the data’ to be considered in the vote.


Summary of themes from discussion of the vote:

  • What is being disputed is about the effect
  • Curious about the data in the global market
  • Testimony from the families is compelling but it difficult to think about that quantitatively – seems best to wait
  • Its post hoc analysis of evidence that’s been revealed, not typically one to be fixed on a P value
  • Critical issue was that there was not a clear effect when subsequent studies where developed based on benefit of post-hoc data analysis from previous study
  • Public testimony was compelling, data was disappointing, I hope we will go forward with this drug development
  • Statutory threshold of efficacy and safety to be applied before exercising flexibility
  • Data is of interest but post-hoc and meta-analysis was not as convincing because was based on sub-groups
  • Impressive by heart-wrenching testimony and thought that was compelling but if that had occurred with everyone in the study we would not have failed to find measureable results and the testimony wasn’t supported by the data
  • I know the harm of going off on a treatment that turns out not to be effective
  • This could be great but we don’t have the data to support it yet
  • I agree with all that’s been said. I congratulate PTC and the participants in the clinical trials. But the data we have before us in going in the right direction – but is not conclusive enough to support an approval.
  • Clearly an augment need in DMD
  • Discussions today were compelling and there appears to be a trend in the data
  • Encourage PTC to continue working on this in on-going trials
  • Thank the young men for presenting very good data of their experiences
  • hope that it shows its effective and they can get it to market
  • I Read all of the written testimony, 19 were from clinicians – total of 74 pts under their care
  • Spoke to power of testimony about impact of time period when product was withdrawn – loss of function and then function regained when product access returned. Clearly an effect – while not in everyone.

PPMD’s Submissions

Written Testimony: 

Open Public Hearing:

What’s Next?

PPMD has connected with PTC to find out how we can help them between now and the PDUFA date of October 24, 2017. We will continue to work with the FDA to help better the review process in any way that makes sense. And regardless of today’s meeting or the final outcome, we will continue to work with families seeking access to ataluren. Stay tuned for ways you and your family can help.

In many ways, PPMD and PTC have grown up together. PTC has been invested in the Duchenne community for over a decade and today was an opportunity for that history to be shared with the FDA. Families that have been participating in this trial have children – teens and young adults now – who have been on ataluren most of their lives. Think about that. These kids have been on ataluren longer than they haven’t.

Thank you to the heroes of the day – the young men and parents who shared their intimate and long history with this drug. PPMD will continue to bring you updates about this therapy as it becomes available.

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