Duchenne Muscular Dystrophy (DMD) is every parent’s
nightmare. It’s an X-chromosome linked genetic disease that condemns young boys
to paralysis and premature death. At present no therapy is available. However,
recent research has indicated that certain types of antisense oligonucleotides
can partially correct the genetic defect and at least slow the course of the
disease. A small-scale clinical trial of an antisense molecule called Eteplirsen was recently completed by the biotech company
Sarepta. The trial involved only twelve boys, but showed encouraging results.
Sarepta then asked the FDA for ‘accelerated approval’ of the drug. This is a relatively new mechanism whereby
the FDA can conditionally approve new drugs for which there is a major unmet
need, such as is the case in DMD. If the drug fails in subsequent larger-scale
trials it would then lose approval. However, the FDA declined and has insisted
on a full-scale placebo controlled trial of Eteplirsen prior to approval (1).
These decisions are always difficult. Clearly it is
the duty of the FDA to make sure that approved medications actually work and
are not a threat because of toxicity. However, stringent requirements for
‘classic’ clinical trials can keep good drugs out of the hands of needy patients
for years. Similar situations have cropped up in the cancer therapy area where
patients have pleaded for promising new drugs before these agents had completed
formal clinical trials (2).
There is a lot of interest currently in adaptive
clinical trials where advanced Bayesian statistics can be used to modulate
trial design as information is accrued, rather than to be stuck with a rigid
trial framework based on initial assumptions. One would think that the
‘accelerated approval’ process could be linked to trials of that type.
In this case it seems that FDA unnecessarily erred on
the side of caution. While it is important to protect patients against possible
toxicities of new drugs, in the case of Eteplirsen there was no evidence of
toxic effects among the boys treated. Thus it seems likely that little harm
would be done by letting additional patients be treated while more was being
learned about the drug.
(1)
(2)
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