Regulatory Focus™ > News Articles > NCATS' Development Program Looks to Avoid Regulatory Hurdles for Once-Abandoned Drugs

NCATS' Development Program Looks to Avoid Regulatory Hurdles for Once-Abandoned Drugs

Posted 18 June 2013 | By Alexander Gaffney, RAC

In 2011, the director of the National Institutes of Health (NIH) reorganized several of his agency's departments into a new center, one intended to upend how pharmaceutical products reach the market by focusing on common bottlenecks, regulatory problems and overlooked compounds. Known as the National Center for Advancing Translational Sciences (NCATS), the center immediately started unveiling big initiatives, including one in May 2012 called the Discovering New Therapeutic Uses for Existing (DNTUEM) Molecules program.

Now, more than a year later, that program is bearing fruit in the form of nine new research agreements meant to see if once-discarded drug compounds can make a clinical difference in the lives of patients.


As unveiled in in 2012, the DNTUEM program was set up to expedite the process by which companies share information. Whereas previous pre-competitive partnerships relied on legal agreements to be set up on a case-by-case basis, NCATS developed template legal agreements to accelerate the application process while providing an adequate level of legal protection.

In an interview with Focus in 2013, NCATS director Christopher Austin said the agreements themselves could take years off the development process.

"When I was at Merck, the biggest problem was in drawing up a collaborative research agreement with an academic organization with which we wanted to work. Sometimes it would take two years to develop a collaborative research agreement," Austin recounted.

"By the time the agreement got signed, the program was very frequently no longer of interest to either party, and many of the people were no longer at those institutions anymore," he continued. "So the lawyers would come to us very proudly-'We've finally got the agreement signed!'-and there's nobody to do the program because science moves on, the question is no longer relevant, or the people are no longer there! There's a huge amount of wheel-spinning that happened, and continues to happen, at these organizations because of not scientific issues, but collaborative problems."

To solve this, Austin and the rest of NCATS put together template agreements to expedite what was ordinarily a long and contentious process.

Industry Partnerships

When the program first launched, NCATS touted the involvement of three major drug developers: Pfizer, Eli Lilly and AstraZeneca, which together promised to supply NCATS with "dozens of their compounds" to get the program up and running. Those compounds were not just any failed molecules, however. Rather, they were ones that had failed in Phase III testing for reasons of efficacy - not safety problems. That means that hypothetically, all NCATS needs to do is find a disease population for which the compounding would be efficacious, and wouldn't have to worry about safety issues sinking the project, which is a major risk in traditional development models.

In the ensuing months, additional partners signed onto the program, including AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Janssen and Sanofi.

The basic premise of their participation was that all drug compounds would remain the property of the participating organizations, while academic researchers will own any intellectual property discovered and may publish the results of their studies. In other words, there's essentially no downside for any entity involved, and manufacturers would have the option to license a discovery to rapidly put it into production.

New Awards

In the intervening months, little has been said about the program or how it's progressing. When Focus spoke to Austin in May 2013, he said NCATS was in the process of going back to investigators who had submitted applications to study the drugs in a particular context and confirming their participation.

And now, thanks to an 18 June 2013 announcement by NCATS, we know who those investigators are and what they will be studying.

"Each award recipient will test a selected compound for its effectiveness against a previously unexplored disease or condition," NCATS explained in a statement, noting that eight diseases are set to be studied:

  • alcohol dependence
  • Alzheimer's disease
  • calcific aortic valve stenosis
  • nicotine dependence
  • peripheral artery disease
  • schizophrenia
  • Duchenne muscular dystrophy
  • lymphangioleiomyomatosis

So far compounds from Eli Lilly (1), AstraZeneca (3), Pfizer (2), Janssen (1) and Sanofi (2) will be studied, leaving AbbVie, BMS, and GSK's compounds by the wayside for now. The studies will be supported by $12.7 million in funding.

What remains to be seen, however, is whether or not any of the compounds being studied will eventually make it to patients. Austin noted in his interview with Focus that NCATS doesn't have the budget to take compounds through clinical testing, and instead acts as an incubator of promising compounds, de-risking the process for later development by larger pharmaceutical and biotechnology companies.

Given the 95% failure rate across all discovered, compounds - and we should reiterate that these drugs are already defined as having failed - the success of even one may be seen as a victory for NCATS.

NCATS Announcement on DNTUEM

Focus' Interview With Chris Austin

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