The Jett Foundation Fighting Duchenne Muscular Dystrophy

What Does the FDA Communicate?

February 3, 2016

Christine, Mindy and I have been meeting behind closed doors and over
the phone with the FDA for quite some time now, about four years and
between the official meetings and impromptu phone calls our
interactions number in the 20s, 30s even? I’ve lost count.

Unfortunately, the FDA seems to communicate differently in our
meetings than guidance they provide to the company. This has led to
accusations that either the FDA is placating our small group of “moms”
or that we are just hearing what we want to hear… We have always
prided ourselves on reporting back to our Duchenne community exactly
what the FDA told us, because we think it is important for them and
even entire rare disease community to know how the FDA is evaluating
new drugs, this process affects us all. I know that what we reported was
accurate, we took amazing notes, double checked with each other and
other stake holders in the room, yet when I read the eteplirsen briefing
document so many things jumped out as being contradictory to what we
had been told, but one line particularly upset me. The briefing document
states

“As the duration of exposure in Study 202 increased, the applicant
proposed comparing the clinical course of treated patients to historical
controls. FDA expressed strong reservations regarding the potential
interpretability of the applicant’s proposed comparison to historical
controls, and the use of 6MWT as the primary endpoint in such a
historical comparison.”

Basically the FDA is clearly stating that they warned Sarepta not use a
historical control. This obviously didn’t sit well with me because I know
in the DMD draft guidance first initiated by Parent Project Muscular
Dystrophy, and then adopted and published by the FDA, a historical
control was cited as a potential path to approval. Then I remember an
unprecedented FDA letter to the Duchenne community following a
particularly devastating blow to the community, in this letter the FDA
states,

“FDA has also been consistent in its guidance to Sarepta that it would be
necessary to submit data from the ongoing open-label trial of eteplirsen
(Study 202) in an NDA, along with data from natural history studies that
could show that patients treated with eteplirsen experienced slower
decline in physical function. FDA has worked closely with Sarepta in
efforts to obtain these natural history data from investigators.”

You can read the entire letter here, if you’d like http://www.fda.gov/Drugs/
So, this means that FDA actually suggested that Sarepta get natural
history data, and, in fact would help them get it because it was so
important. Did I misunderstand something again? I think the entire
Duchenne community has gotten a true glimpse of FDA
communications, and we should all be deeply troubled by it. These two
statements are so contradictory they cannot be reconciled. It would be
extremely troubling if someone in the division was unaware that they
requested this data from Sarepta, it would be even more troubling if
someone was aware that the agency did ask for the data but chose to
misrepresent this fact in the briefing document. These are our children,
the majority of whom have been declining for over 4 years without
treatment.

FDA has the authority-and a specific mandate from Congress-to exercise
flexibility when assessing drugs for rare disease. FDA gave clear
guidance to the Duchenne community about the importance of the
natural history data. Therefor it is not a choice for a reviewer to ignore
or disregard this data. These are our children, the majority of whom
have declined over four years without treatment, while waiting for this
data. Whoever is responsible for writing the briefing document, and
whoever signed off on it should be ashamed of the conflicting
information contained in it and the guidance given to the community.

This time, it isn’t just the 3 of us who heard it, this time, the whole world is watching.

Jenn McNary, Director of Outreach & Advocacy,
Mom to Austin & Max

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