May 12, 2023
I’m Dr. Diana Zuckerman, president of the National Center for Health Research.
Our nonprofit think tank scrutinizes research on the safety and effectiveness of
medical products and we do not accept funding from companies that make those
products. So we have no conflicts of interest.
Duchenne Muscular Dystrophy is a terrible, terrible disease. Patients and their
families deserve an affordable treatment that is proven to be safe and effective.
If the evidence doesn’t meet FDA standards because a study is not well designed
or the clinical results are in the right direction but not statistically significant, then
patients should have access to experimental treatments at cost, through the
FDA’s expanded access program.
As a parent and scientist who conducted research at Harvard and Yale, I wish the
data were more persuasive. Unfortunately, Sarepta has a track record of 3 DMD
accelerated approvals based on questionable data that have never been
confirmed in required post-market studies. One confirmatory study was not even
started for 5 years after being sold under accelerated approval.
Sarepta’s one randomized clinical trial includes only 20 boys who received SRP-
9001 and 21 boys on placebo. The analyses did not show significant differences in
motor function in patients receiving the drug compared to controls at week 48.
We’ve seen moving videos of boys who have done well on 9001, but it is clear
that these individual examples are not consistent with the scientific data. The
data indicates that there are boys doing as well on placebo, and boys on 9001
who are doing poorly.
And although the sponsor is seeking accelerated approval based on a biomarker,
the randomized trial found that those protein levels at week 12 did not correlate
with muscle function at week 48.
We agree with the FDA that since the engineered molecule contains less than half
of the structure of natural dystrophin, its value as a surrogate endpoint is NOT
known. The correlation only reached statistical significance in an open label
portion of the study, which as we all know is biased and merely hypothesis-
generating, rather than scientifically valid.
Safety issues of gene therapy are well known. Some gene therapy patients have
died.
Equally important are the ethical issues a panel member brought up this morning.
If this drug is granted accelerated approval, it is unlikely that the confirmatory
study that is almost done will in fact ever be appropriately completed, because
placebo patients will switch to treatment.
In conclusion, there is an unmet need for effective treatment, but there are
already 4 treatments for DMD on the market, none of which have been proven to
work. In fact, European and Canadian regulatory agencies have not approved
those DMD drugs. If the FDA no longer represents the gold standard for approval,
that poses risks for all Americans with serious diseases.