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NCATS Looks to the Crowd to Find Matches for Failed Drugs

By Mari Serebrov
Washington Editor

WASHINGTON – When it comes to discovering new uses for failed drugs, serendipity is about to be replaced by translational science in what National Institutes of Health (NIH) Director Francis Collins is calling a "win-win-win" pilot program for researchers, industry and patients.

Under the crowd-sourcing program, NIH's National Center for Advancing Translational Sciences (NCATS) will serve as the matchmaker – hooking up failed compounds with researchers who might find new uses for them. To make the research more enticing, NCATS will offer researchers a share of $20 million in two- and three-year grants, to be awarded next year.

The pilot will start with 24 compounds that have been shelved by AstraZeneca plc, Eli Lilly and Co. and Pfizer Inc. All of the compounds, which could cover a broad range of conditions, are Phase I or II candidates that the companies "de-prioritized" for business reasons or lack of efficacy in a desired indication.

The pharma companies will make the compounds – along with toxicity, dosing and biomarker data – available to interested researchers.

The companies will retain their intellectual property (IP), but researchers will have the rights to IP they develop. The pharma companies would then have first rights at licensing that IP.

To help with the matchmaking, the program includes template pre-nups that will speed negotiations between industry and researchers, Collins said, noting that negotiations often get bogged down, slowing drug development.

In the past, finding new uses for old drugs was serendipitous at best. One of the big success stories was azidothymidine (AZT), which failed to show efficacy against cancer. But 25 years later, it was approved as the first HIV drug, opening the door to subsequent HIV therapies.

It's time to stop relying on serendipity, Collins said. "We need to generate more of these success stories in a more systemic manner," he added.

Because the compounds have already been studied and their targets are known, the initiative will not involve guesswork. Collins noted that researchers, in recent years, have identified the causes of more than 4,500 diseases. The hope is to marry the right compound to one or more of those diseases.

One obstacle to transforming failed drugs into new cures was lack of information. Drug companies generally don't share all the data from failed trials. And they aren't privy to unpublished scientific advances being made at research institutions. The idea behind the NCATS initiative is to share that information.

The initiative is partly an outgrowth of a research agreement Pfizer had with a university. The company realized the next step was to make the data available to a broader group of researchers, said Rod MacKenzie, head of worldwide research at Pfizer.

"Too many times, these compounds end up sitting on shelves or in somebody's freezer," he said at a media briefing.

Besides contributing compounds, AstraZeneca kicked in experience it gained from a similar collaboration with the UK's Medical Research Council. Eli Lilly signed on six weeks ago as a natural elongation of its current agreement with NIH to screen compounds.

As the program progresses, Collins said he hopes more pharma companies will get involved. And in the future, the initiative may expand to repurposing approved drugs, as well as the compounds that failed.

The initiative was welcomed by the research community. "I think it's an excellent idea," George Painter, director of the Emory Institute for Drug Development, told BioWorld Today. "It's encouraging that everyone's beginning to understand that a more cooperative environment is necessary" to get new therapies to patients.

Progress Made in Drug Shortages

Voluntary early notification is paying off in averting some drug shortages.

Following an executive order last October and the FDA's efforts to encourage drugmakers to inform the agency of potential shortages as early as possible, there has been a sixfold increase in early notifications from manufacturers, according to FDA Commissioner Margaret Hamburg. (See BioWorld Today, Nov. 1, 2011.)

"Also in that six-month time frame, we have been able to prevent 128 drug shortages, and we're seeing fewer numbers of shortages occur – 42 new drugs in shortage reported in 2012, compared to 90 new shortages at this time last year," she said.

Meanwhile, the FDA is trying to address existing shortages. For instance, it's working with Teva Pharmaceutical Industries Inc. to improve supplies of leucovorin injection, a cancer drug used with methotrexate for children with a serious form of leukemia. The FDA expects additional shipments in the coming weeks.

The agency also is working with Lundbeck Inc., the sole supplier of Mustargen (mechlorethamine HCl), to resume production of the cancer drug.

Hamburg said Lundbeck plans to have Mustargen available again by August. It has been in short supply for the past two years.