When scientists with the pharmaceutical company Pfizer started clinical trials in 1991 on a chemical compound named UK-92480, they aimed to show the drug’s potential therapeutic benefit for a cardiovascular condition caused by restricted blood flow to the heart muscle.
Less than two years later, hope that the compound, now better known as sildenafil, could treat angina began to fade.

But the drug wasn’t shelved. Rather, scientists began exploring whether one of the drug’s reported side effects—erections—could help men suffering from another condition.

The U.S. Food and Drug Administration in 1998 approved sildenafil, under the brand name Viagra, for the treatment of erectile dysfunction. In its first year on the market, sales of the little blue pill topped $1 billion.

The transformation of sildenafil into a treatment that’s now been prescribed to tens of millions of men around the world is one of the most well-known examples of a practice known as drug repurposing. The practice isn’t new but it is becoming an increasingly attractive option for academic and pharmaceutical industry researchers, as well as nonprofit organizations and patient advocacy groups—all of whom are seeking ways to cut the time and expense involved in getting new treatments to market.

Winning approval for a new drug takes about 14 years on average and costs can exceed $2 billion, according to data from the National Center for Advancing Translational Sciences, or NCATS. The failure rate in the drug development process, meanwhile, is 95 percent.
That leaves a vast pool of partially developed chemical compounds that could potentially be tapped for uses other than which they were originally intended. Those repurposed drugs could move to market in less time and for less money than it takes to gain approval for novel drugs by skipping preclinical testing requirements and, possibly, Phase 1 safety and dosing trials.

The ability to bypass those stages means a repurposed drug could make it to market in only four years and at a fraction of the cost of a brand new treatment, according to Cures Within Reach. The Illinois-based nonprofit group, which supports medical repurposing research, also notes that the “risks are better known and the chance of failure due to adverse side effects is reduced” with repurposed drugs.

While serendipity has largely driven the repurposing of drugs in the past, more deliberate approaches to this practice have been recently developed in a bid to fuel more collaboration between stakeholders and hasten the development of new therapies.  

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In 2012, NCATS, an arm of the National Institutes of Health, launched a program called Discovering New Therapeutic Uses for Existing Molecules that makes proprietary drugs that have undergone significant research and development by pharmaceutical companies available to academic researchers.

Christine Colvis, the director of drug development partnership programs for NCATS, called drug repurposing “a viable strategy for developing new therapies” and one that is generating more interest and engagement from academic institutions and academic investigators.

“There are so many diseases for which there are no treatments or for which current treatments are not adequate or don’t treat all of the patient population,” Colvis, whose team leads the New Therapeutic Uses program, said. “There is just so much unmet medical need out there and when there’s something for a scientist, for a researcher, that’s sort of staring them in the face as a potential thing that could make a difference in people’s lives, it’s hard for them not to pursue that path.”

Colvis pointed to research by neurologist Stephen Strit­tmatter of Yale University as one promising example of collaboration between academia and industry that NCATS is supporting.

Strittmatter and his colleagues in 2012 published a paper that suggested blocking a protein called Fyn kinase may help treat Alzheimer’s disease. Those findings were released around the same time NCATS launched its New Therapeutic Uses program and made a Fyn kinase inhibitor developed by AstraZeneca available to researchers.

AstraZeneca had developed the drug, called saracatinib, to treat cancer. Strittmatter and his colleagues submitted a proposal to test saracatinib as a treatment for Alzheimer’s-related brain abnormalities and received one of the first New Therapeutic Uses awards in June 2013.

The research team was able to begin a Phase 2a human clinical trial of saracatinib within about 18 months, compared to the decade it can take to move a new treatment to that stage.

“Had AstraZeneca not put that drug on our list of drugs that would be available, we still wouldn’t be investigating this as a potential target for Alzheimer’s disease, and had Dr. Strittmatter not published his paper or had he not seen our funding opportunity announcement, still nothing would be happening,” Colvis said. “But instead now we are in the final year of a Phase 2 trial and hope to see those results in about a year from now.”

NCATS, in collaboration with AstraZeneca and Janssen Research & Development, LLC, in February announced it was offering $6 million in funding to support additional public-private partnerships between the biomedical research community and pharmaceutical companies. Other NCATS partners for this program include AstraZeneca subsidiary MedImmune, AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Pfizer and Sanofi.

Colvis said the types of partnerships NCATS is helping foster are “really just trying to demonstrate a strategy. Our real hope is that other entities start to use this model and this strategy.”

“We hope to see this model used around the world in order to really have an impact on health,” she said.

While Colvis describes NCATS’ efforts to promote drug repurposing as “disease agnostic,” other groups are embracing the practice in an attempt to find treatments for a specific group of conditions: rare diseases.

Findacure, a charity based in Cambridge, England, is working to develop a model to support repurposing existing, generic drugs to help treat patients suffering from conditions that affect fewer than 1 in 2,000 people. (In the United States, a rare disease is defined as a condition affecting fewer than 200,000 people at any given time).

“It’s a type of research that can be delivered more cheaply and more quickly and that’s really important in the rare disease space,” said Rick Thompson, Findacure’s head of research.

Of the more than 7,000 rare diseases, only around 400 have licensed treatments, according to Findacure. Thompson said it’s difficult for the pharmaceutical industry to actively repurpose generic drugs for rare diseases for two reasons: a lack of profitability due to the small patient population and the difficulty to secure intellectual property.

Findacure has developed a new mechanism called the Rare Disease Drug Repurposing Social Impact Bond in an effort to address that gap. The model, which Findacure has been working with Cures Within Reach to develop, would use money the National Health Services in the U.K. saves by treating patients who have rare diseases with repurposed, generic drugs to reimburse the cost of clinical trials that prove the effect of such drugs.

“It’s securing returns based on money that’s been saved rather than delivering a high drug price,” Thompson said. The charity has completed a proof of concept study for its model and is now working toward developing a full business plan.

Meanwhile, the group recently launched an open call for drug repurposing ideas for rare diseases in partnership with Cures Within Reach and Healx of Cambridge, England.

The open call project aims to “demonstrate the huge potential of clinic-led, patient group-led, and researcher-driven innovation in drug repurposing for rare diseases” and show “the need for new funding streams to help these ideas bridge the translational gap,” like Findacure’s Rare Disease Drug Repurposing Social impact Bond.

“We think this has real potential to promote and allow this type of generic drug repurposing in the rare disease space to move forward,” Thompson said. “We need some kind of innovation in this space to encourage this type of work.”