US drive to speed trials for rare disorders

washington

The US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) are launching an initiative to make clinical trials for rare illnesses speedier, less cumbersome and less costly.

The FDA and NIH aim to promote research on gene therapies for rare disorders by luring more investigators into the area and encouraging industry to support research in clinical areas that do not have a big market.

The NIH has received 259 applications for gene therapy protocols in the past ten years. But few involve rare diseases, even though gene therapy was conceived to treat rare, inherited disorders due to mutations in a single gene. These ‘monogenic’ diseases are increasingly ignored as scientists and their industry sponsors focus on developing gene therapies for large-market diseases such as AIDS and cancer.

Only 34 protocols have been for monogenic diseases. By contrast, 61 per cent have been for cancer. And the trend is growing more marked. Of 31 protocols submitted so far in 1998, two are for monogenic diseases while 22 are for cancer.

Figure 1

Protocols submitted to the NIH Recombinant DNA Advisory Committee, 1988-98.

“All the money is going into the most profitable diseases⃛ so it's obviously an area that the government has to step into,” says Abbey Meyers, the president of the National Organization for Rare Disorders.

Philip Noguchi, the director of FDA's Division of Cellular and Gene Therapies, says gene therapy's “focus [on rare diseases] has drifted over the last few years. This [new initiative] is an attempt to bring it back.”

A working group from the FDA's Center for Biologics Evaluation and Research and the NIH's Office of Rare Diseases is developing a strategy to speed up trials.

First, it wants to relieve investigators of the need to reinvent the wheel each time they apply to do a gene therapy experiment. Currently, each investigator must prove a given vector is safe for a proposed therapy. The group hopes to demonstrate through NIH-funded studies that a particular vector is broadly safe so investigators will not have to demonstrate its safety separately.

Second, the group proposes that the FDA accepts protocols with as few patients as possible and merges safety and efficacy studies, which are conducted in separate stages.

Even if the initiative greatly reduces the early development costs for companies, however, there remains little incentive to commercialize for small target populations. James Wilson, the director of the Institute for Human Gene Therapy at the University of Pennsylvania, says he is “afraid we will still be left with some diseases in which we can't encourage anybody to do it”.