I have never been so proud of this community. Today our community reached a historic milestone, a moment I wondered if we would ever see. Today’s FDA Advisory Committee (Ad Comm) for BioMarin’s drisapersen, gave us an up close look at the regulatory process, learning firsthand what the FDA considers most important when reviewing potential therapies in rare disease. It also gave us an opportunity to share our stories, our experiences with this therapy, whatever that experience was – many seeing improvement, some seeing side effects, but all having the ability to weigh the benefit/risk equation as a family with their medical provider. I think that was the takeaway. I think that’s the script we all spoke from, in a variety of ways, based on a variety of firsthand knowledge – WE WANT OPTIONS.


Voting Results

Today’s final discussion and vote are similar to scenarios we discussed in last week’s webinar with the agency challenging the Sponsor (BioMarin) on the data presented, as was anticipated by the briefing documents the FDA published last Friday, which included their questions. Questions 1-8 were presented in pairs with a discussion question followed by a vote on that discussion. In total, Ad Comm members each voted 4 times. The FDA did pose one last question to the Ad Comm that had not been previously made public (Question 9), and concluded the proceeding by asking each member of the committee to address the question, though no official vote was taken.

The questions, as well as the votes, were designed to facilitate discussion around the findings and complexities of each of the three studies that had been presented throughout the day. Discussion questions included considerations of efficacy evidence of each of the studies, efficacy as related to the statistical significance in both the primary and secondary endpoints, and evidence of dystrophin production and relevance on interpretation on clinical results.

Question #2: What overall impact do the issues discussed in question #1 have on the persuasiveness of Study 1?

  • A Strengthen – 1
  • B Weaken – 9
  • C. No Effect – 7

Themes that arose from the explanations from the various Ad Comm members as they explained the reasoning for their votes included:

  • Concerns that the secondary endpoints did not seem to be 'pointing in the right direction’ and lacked statistical significance
  • Concerns over the small data set
  • Suggestions that the study length should have been longer to allow more time for effect to be detected
  • Concerns about the absence of efficacy, despite the treatment half-life and expected plasma concentrations

Question #4: What overall impact do the issues discussed in #2 have on the persuasiveness of Study 2?

  • A. Strengthen – 0
  • B. Weaken – 5
  • C. No Effect – 12

Themes that arose from the explanations from the various Ad Comm members as they explained the reasoning for their votes on Question 4 included:

  • Small sample size
  • Many voiced concerns that the results were sensitive to the findings of one patient (speaks to the trial size/ power of the study)
  • Some of the Ad Comm members expressed clarity in their impression that the 3 mg/kg dose did not work as well as the 6 mg/kg dose

Question #6: What is the impact of Study 3 results on the persuasiveness of findings in Study 1 and Study 2?

  • A. Strengthen - 0
  • B. Weaken – 15
  • C. No effect – 2

Themes that arose from the explanations from the various Ad Comm members as the explained their votes on Question 6 included:

  • The results were not statistically significant
  • This well designed, Phase III study failed to meet its endpoint

Question #8: What is the impact of the dystrophin results on the interpretation of the clinical results?

  • A. Strengthen – 0
  • B. Weaken - 6
  • C. No Effect – 10
  • No vote – 1 (one Ad Comm member left before the vote)

Themes that arose from the explanations from the various Ad Comm members as the explained their votes on Question 8 included:

  • This is a targeted therapy that should have demonstrated a dystrophin effect
  • Several members of the Advisory Committee emphasized concern that biopsies were taken from members of the Duchenne community with little yield

During the course of discussion, a question arose about the study population and potential for extrapolation and application of this therapy (if approved) to a broader segment of the Duchenne community. Dr. Ron Farkas from the FDA responded by acknowledging that  - while discussing the specifics of labeling is a bit difficult -  in a recent effort with Parent Project Muscular Dystrophy, the FDA had released guidance saying that they would consider the broadest application of the population possible, in the context of benefit risk.


Question 9:

“In light of today’s discussions, please discuss the overall strengths and weaknesses of the data supporting the efficacy of drisapersen and the acceptability of its safety profile for the treatment of Duchenne muscular dystrophy amenable to exon 51 skipping.

The discussion around this question raised many important safety considerations and allowed for each member of the Advisory Committee to make a summary remark.

While the votes are discouraging, they are only recommendations and are not necessarily reflective of how the FDA will ultimately rule.

After the Ad Comm: What’s Next?

We don’t know what the final outcome for drisapersen will be. Based on the requirements by PDUFA, the FDA is required to tell BioMarin something on or about December 27. I struggle with what to make of today, of what the outcome will be, and quite frankly what result is best for our community. But like I said in my testimony, I believe in options with caveats/labeling that accounts for safety and with the consultation of physicians. I am confident that we provided the FDA with plenty of information to make an informed decision.


Regardless of outcome, this community should be proud…Proud of every person in this community who stood up at that microphone today in a room full of decision makers and told their story, spoke their truth, and shared their lived experience of this diagnosis. Proud of every person who submitted written testimony asking the agency to consider an approval. But most importantly, we should be proud of the incredibly brave young men and their families who participated in this trial. They are our strength. And they are why we continue to work tirelessly to end Duchenne.


We will continue to keep you updated on any information that comes out of the FDA regarding decisions or next steps with drisapersen and hope to have more formal details in the coming week regarding eteplirsen's Ad Comm.

PPMD's Submissions

Written Testimony:

Click here to download the written testimony submitted by PPMD President Pat Furlong to the Peripheral and Central Nervous System Drug Advisory Committee.

Open Public Hearing Testimony:

Pat Furlong, Parent Project Muscular Dystrophy.

Parents and patients carry the heaviest burden. It is an honor and privilege to be here today.

I have no financial disclosures to report, no investments in any company developing drugs or biologics for Duchenne, not personally or professionally.

3.5 minutes is a very short time to discuss a lifetime of experience with Duchenne. During the last 30 years, I have met more than 5000 families from around the world. Each has their own story, one of observing delay of milestones that every parent wants and needs to see as their child grows, increasing concern about a child’s tired legs’ or his struggles on steps. Many of those same families experience an odyssey of diagnosis of months to years, when finally, a physician in some small office mentions the word Duchenne and spreads the Tarot cards predicting a future of decline and death. Day by day we have watched as our children gain strength, marking and celebrating those precious days, only to watch those milestones disappear:

  • Walking
  • The ability to manage personal needs
  • Lifting arms to face
  • Breathing
  • And finally, for many of us, watching our son lowered into the ground.

My sons were diagnosed in 1984. They died at 15 and 17, just 7 months to the day apart. At that time, individuals with Duchenne had no options. None. Each of us live with the words ‘if only’… on a feedback loop, wishing for knowledge, understanding, options and the ability to turn back time.

Duchenne has a perfect record of lives claimed.

In an effort to understand the collective voice of the Duchenne community, PPMD conducted a pilot study to explore Caregiver Preferences - (in this case, parents) because we believe it is important to ensure Regulatory Agencies and Advisory Committees are well informed about benefit and risk in Duchenne. The study found that caregivers believed that they carried significant risk with the diagnosis and were willing to accept additional risk to achieve their highest priority… slowing progression…. Even above extending life 3-5 years.

Clearly, all of us make risk/benefit decisions every day of our lives: when we drive a car, cross the street, attend a concert in Paris. With a diagnosis of Duchenne, these decisions are daily. Parents identify clinicians they trust who will be able to guide them in making these decisions about benefit, risk, and uncertainty.

How many of us have asked, “Doctor, if this was your son, what would you do?”

Today we are here to discuss drisapersen. The decision to recommend drisapersen is a monumental responsibility for all of us. You are hearing stories on both sides, from families who have seen positive changes in their son and from families who made different benefit and risk calculations out of necessity. Each of the families today are testifying as an N=1 experience.

Today, the community has had a comprehensive exposure to the data and a collective exposure to the patient experience. Every family must weigh benefit and risk in the context of their lives. Now, we ask you today to weigh carefully the data, consider the risks we, as families, must carry as you consider the potential benefits and risk of drisapersen.

As a community, we want and need safe and effective drugs. We are looking for options that provide meaningful benefit – more days to keep up with friends; more days to be independent, to walk up a step, to breathe without the need for assist devices.

As a community we want options, an arsenal of weapons at our fingertips so that we can fight to end Duchenne, head on. We ask the agency and this committee to weigh the data against the lived experience of families. A recommendation for approval today would be a start, albeit with the caveats of limited use and safety concerns. But it is a starting point, one option and one that could lead the way.


Learn more

For more information about the FDA Ad Comms, please visit the links and resources that we at PPMD have compiled over the past few months with the assistance of our community members, regulatory advisors, and federal agency partners:

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Comment by Hassan K. Shehu Shehu on November 25, 2015 at 5:43am
Please we want to know whether our child can try this drugs we see on the ppmd post , because the boy is on predinenselone for over 2years.
Comment by Jason Darienzo on November 24, 2015 at 8:52pm

Watching today From about noon I was astonished by the FDA's lack of preparedness.   It appeared they had no understanding of the disease and the drug they are reviewing.  There didn't even seem to be any continuity to the previous recommendations made by the FDA themselves.  I don't know if it was addressed before I started watching, but there was no talk about natural history data or any data beyond 48 weeks there is over 200 weeks of data.  It's been 3 years since the 48 week phase III study ended. I don't know what the FDA will do with Drisapersen but it don't look good to me.  Both Drisapersen & Eteplirsen address exon 51 but are conpleatly different compounds. We patients and parents must insist they be treated independently and all 3 years of data (efficacy not just safety) get looked at and discussed in public by the FDA.  We have one more shot with Eteplirsen before we may have to redo the whole clinical trial process.  


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