By AMY DOCKSER MARCUS
A government program focusing on rare diseases has launched five pilot projects that are taking the National Institutes of Health in a new direction: developing drugs.

The NIH Therapeutics for Rare and Neglected Diseases (TRND) program was established last year with $24 million of funding. TRND will work together with scientists, advocates and others to do the required research and testing on drugs before a compound can be tried in humans in a clinical trial.

Promising new drugs discovered through basic research often flounder during this stage of the process, which is expensive, time-consuming and prone to failure.

The pilot projects, three of which were selected this spring, target drug development for sickle-cell disease; chronic lymphocytic leukemia; the fatal neurodegenerative disease Niemann-Pick Type C; the genetic muscle disorder hereditary inclusion body myopathy; and the parasitic diseases schistosomiasis and hookworm.

The projects, which are in various stages of development, were selected because they illustrate a range of problems and issues in the effort to drive drug development.

The problems include the high cost of studies in animals to determine if a drug is too toxic to give to humans, the challenges of meeting regulatory requirements before the Food and Drug Administration allows clinical trials to begin, and the sheer amount of coordination that goes into getting a new drug to market.

"Most of the problems we are addressing are not scientific problems," said Christopher P. Austin, director of the NIH program. "They are operational issues."

For most new drugs, these issues are handled by a pharmaceutical company. Rare diseases, which the NIH defines as diseases that affect fewer than 200,000 people in the U.S., represent a small market.

As a result of the small markets, many pharmaceutical companies are reluctant to take on the risks and expense of trying to develop new drugs for these conditions.

TRND is assigning project managers with experience in drug development to the pilot projects to help identify the necessary steps to get to clinical trials.

The sickle-cell disease project, for instance, involves AesRx LLC, a Newton, Mass., biotech company, and needs to complete toxicity studies and regulatory work to launch a trial.

"The alternative would be to raise outside capital from venture capitalists,'' said Steve Seiler, chief executive of AesRx. Mr. Seiler said at this stage of the project it would have been difficult to get the financing. "Once we have human clinical data, it is much different,'' he said.

With the muscle disorder hereditary inclusion body myopathy, William A. Gahl, clinical director of the National Human Genome Research Institute, said he had been unable to launch a clinical trial to test a promising compound for three years, before the project was taken up by the NIH program.

He said that before he could start a clinical trial with the compound, the FDA wanted toxicology studies conducted in animals, at an estimated cost of $500,000 to $1.5 million—money the small biotech company and patient advocacy group he is working with didn't have available. "We were about to give up," Dr. Gahl said.

TRND is getting toxicology studies done and has hired a regulatory consultant to help address any regulatory issues with the FDA to get permission to start a trial.

"TRND has smoothed the way enormously," said Dr. Gahl, who said he hopes to launch the trial this year.

In the case of Niemann-Pick Type C, TRND's Dr. Austin had previously worked with a group of scientists and parent funders called SOAR-NPC to screen already approved FDA compounds to see if they might be effective against the disease. A promising compound was identified, but extensive work will be required to determine whether the drug is safe and effective enough to be tried in patients, Dr. Austin said.

This kind of tinkering with a promising drug—testing it in animals and then going back to the lab for further tweaks—is both time-consuming and expensive, and can be out of the reach of a parent-funded organization like SOAR.

Last week, at the annual conference of the advocacy group Genetic Alliance, Dr. Austin, a parent funder in SOAR, and Steven U. Walkley, a professor at Albert Einstein College of Medicine who is a member of SOAR, gave a joint talk that addressed some of the pressures the NIH program faces.

"There is a lot of promise built in to TRND, but there is no guarantee that they will be able to make the science deliver a therapy for a disease," Dr. Walkley said.

Dr. Austin said he recognized that "we have to succeed with these pilot projects, and if we don't, the program won't continue."

Half of the program's budget this year is going to fund the five pilot projects, he said. The other half of the budget is going to setting up TRND. Dr. Austin added that the program plans to solicit additional projects in September.

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