WASHINGTON, D.C. - The statistics on drug development are no secret: for every 10,000 compounds discovered, only one gets approved, and it usually takes 14 years and $1.2 billion to reach the market. "Surely there must be bottlenecks that can be tackled," National Institutes of Health Director Francis Collins said in a speech Monday at the AAPS annual meeting.
Collins told the gathering of pharmaceutical scientists his agency needs to take an engineering approach to eliminate anything that slows development. Early discovery and preclinical development are well-known bottlenecks, and Collins said identifying new targets for approved drugs or compounds abandoned in the clinical stage will help the industry get more drugs to market.
Target identification is fundamentally important to bringing a drug to market. "If you don't get that right, what comes after isn't likely to be successful," observed Collins. Advances in understanding the molecular basis of diseases have been dramatic--such roots of 4,500 diseases have been identified--and could lead to better target identification. In addition, 1,300 variances in the human genome have been associated with heightened risk of certain diseases. Now it's time for researchers to determine whether using these variations as a target is a valid approach for identifying these diseases. Systematically identifying high-quality targets could boost the number of compounds that survive the development process.
The preclinical phase--also known as "the Valley of Death"--is also ripe for new thinking, said Collins. Toxicology is the most common reason for drug development failure, he noted, and improved preclinical tools would give researchers better indications as to whether a compound will be safe in humans. Currently, the industry relies on animal testing, but work is under way to create various tissue types and build them into 3-D structures that could someday be used for more accurate toxicology testing. The NIH has already joined forces with DARPA and the FDA to develop chips to screen for safe, effective drugs. Collins believes that the collaboration--with the FDA's guidance--will eventually enable technology that could be a substitution, not an add-on, for current toxicology testing methods.
Repurposing and rescuing drugs that are already known to be safe in humans presents another opportunity for the industry. The antiretroviral treatment AZT (for HIV/AIDS) and thalomid (for multiple myeloma) are examples of old drugs that learned new tricks. "Many compounds are sitting in freezers waiting for a day they might be repurposed or rescued," Collins said. To that end, the NIH has compiled a definitive list of approved drugs, providing researchers a resource for systematically looking for drugs that may be repurposed for other uses.
To streamline the drug development process, the NIH has proposed the creation of the National Center for Advancing Translational Sciences (NCATS). Collins said the center would catalyze the next generation of innovative methods and technologies that would enhance the development, testing and implementation of diagnostics and therapeutics across a range of human diseases and conditions. NCATS would "look at the pipeline itself as a scientific problem and be a more effective facilitator to resolve those problems," he said.
The Senate is strongly in favor of the proposal, but no bill has been proposed in the House. Collins stressed that the center, which would bring together existing government components and not require any new money, wouldn't be competitive with the private sector. "NIH doesn't want to predict the future of medicine," Collins said, "just enable it."