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.