NIH Center Spearheading New Drugs, Improving R&D Process

While the search for effective and safe new drugs remains painfully slow and expensive, particularly for psychiatric disorders, one of the centers in the National Institutes of Health (NIH) has been chipping away at the fundamental problems of drug development.

Since its inception in 2012, the National Center for Advancing Translational Sciences (NCATS) has done numerous projects to help bring new drugs closer to patients, some of which have moved the neuropsychiatric field forward. For example, the center’s Bridging Interventional Development Gaps (BrIDGs) program has helped Intra-Cellular Therapies Inc., a biotech company, develop and synthesize a phosphodiesterase 1B (PDE1B) inhibitor for clinical trials to treat cognitive dysfunction in schizophrenia. Also, the BriIDGs program has helped RTI International, a company based in North Carolina, develop JDTic, a potent and selective antagonist of the opioid kappa receptor, for human studies. JDTic is a promising candidate for the treatment of cocaine addiction, depression, and schizophrenia.

The role of NCATS, however, is not confined by specific diseases or treatments. Unlike other NIH institutes, the staff of NCATS works across specialties and disciplines.

Collaboration is Obligatory

“[NCATS] is complimentary to the other NIH institutes,” Christopher P. Austin, M.D., director of NCATS, told Psychiatric News. With each project it supports, the center intends to make the drug R&D process faster, more efficient, and less expensive. “Each project has to achieve at least two things: It not only has to move an individual drug target or disease further down the pipeline, but also has to teach us some general principle about translational science,” explained Austin.

NCATS

For example, a grant or collaboration may help move a new drug forward, but it also has to result in a better method to identify drug targets, a new system to predict toxicity, an intervention to improve patient compliance, or a system for less expensive and more effective clinical studies.

To accomplish these goals requires an unprecedented degree of collaboration linking academia and industry, physicians, and patients. Austin acknowledged that the pharmaceutical industry, including not only large pharma companies but also smaller biotechs and venture capital investors, is a main player in this collaboration and a potential beneficiary.

New Use for Old Molecules

The involvement of pharma is highlighted in the New Therapeutic Uses (NTU) program. It’s a platform that allows drug companies and researchers to find each other to research new uses for molecules the companies have shelved because of unsuccessful development. Beyond the platform, NCATS has developed templates and tools—such as confidentiality and licensing agreements—to help both sides negotiate in these collaborations.

“A general problem is that 80 percent of drugs that have been tested in humans are never approved [for marketing] for a variety of reasons,” said Austin. “A huge amount of money has gone into the drug development but is benefiting no one.”

Sometimes a drug candidate is shelved because its efficacy is not competitive enough in a crowded market or the projected profit is deemed not worth the investment. Yet outside researchers may test the drug further for different indications (also known as “drug repurposing”) at no cost to the company with the possibility of success.

In one example, NCATS is supporting a collaboration between Pfizer and John Krystal, M.D., at Yale University to develop a GlyT1 inhibitor to treat cognitive deficits in schizophrenia. In another collaboration, Alan Breier, M.D., at Indiana University is studying an estrogen receptor beta agonist, owned by Eli Lilly, in clinical trials for schizophrenia.

“The endpoint of a successful program is licensing [a molecule] to a company,” said Austin. “We want to do just as much work as possible to convince the company to pick it up” and develop it toward marketing. “And we move on to other projects.”

Entering New Frontiers of Drug Research

Some cutting-edge technologies that promise to greatly expand drug discovery are getting support from NCATS, and the center’s translational perspective may push their use into patient care more rapidly. One such endeavor is the Extracellular RNA Communication program, which may yield critical information about a range of diseases. NCATS is supporting a group of researchers at Oregon Health and Science University in Portland to study the use of microRNAs as biomarkers to diagnose Alzheimer's disease in the early stage.

Although NCATS does not focus on any particular disease, neuropsychiatry “is an area of intense interest for us, because it leads to the highest cost of morbidity worldwide and presents the greatest need,” said Austin, who was trained as a neurologist and previously worked in schizophrenia research in the pharmaceutical industry.

A particular challenge in neuropsychiatry, Austin pointed out, is that “we need new models for studying these diseases.” NCATS is supporting the development and use of tissue chips that can show, in vivid detail, how drugs work in human organs, even the brain. If successful, these chips can greatly improve the efficiency and reduce the cost of new drug development.

Patients First

Patient groups and advocates make up one-third of NCATS’ advisory boards, Austin noted. The push toward faster bench-to-bedside technologies and new drugs carries with it ethical and safety concerns, and the center’s emphasis on patient involvement reflects these concerns.

“We involve patients in our projects from the very beginning,” he said. “Patients are not subjects, but our partners on the research team.” ■