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VUMC’s program to repurpose drugs lands international acclaim

Jul. 23, 2020, 10:03 AM

 

by Bill Snyder

Vanderbilt University Medical Center is attracting international attention for its proposal to repurpose existing drugs for new uses in ways that can dramatically improve access to medicines by billions of people throughout the world.

Project Remedi, which stands for Repurposing Essential Medicines Internationally, is a partnership of VUMC’s Drug Repurposing Program and the Aurum Institute, a leading health care organization based in Johannesburg, South Africa.

The project’s proposal to uncover new uses for generic drugs on the World Health Organization List of Essential Medicines received high praise from WHO officials, according to Gordon Bernard, MD, VUMC Executive Vice President for Research.

Earlier this year the John D. and Catherine T. MacArthur Foundation announced that Project Remedi was among the “Top 100” proposals in its 100&Change competition for a $100 million grant to help solve the world’s most critical societal challenges.

Along with other Top 100 proposals, Project Remedi is now featured prominently in the foundation’s on-line Solutions Bank and its Bold Solutions Network, both of which help philanthropies find investment opportunities for “accelerating” positive social change.

Project Remedi was not among the top six finalists in the 100&Change competition announced on July 20. But “it’s a part of our success to have made it this far,” said Jill Pulley, MBA, who organized and directs VUMC’s Drug Repurposing Program, “because (we now) have visibility to philanthropic donors.”

“The most exciting part of this,” she added, is the consideration of Project Remedi’s proposal by the WHO. The proposal was guided in part by collaborator Devi Sridhar, PhD, founding director of the Global Health Governance Program at the University of Edinburgh in Scotland.

The WHO list currently includes 376 safe and affordable drugs that are considered to be “essential medicines.” More than 150 countries use the list to guide treatment decisions. Yet the medicines on the list are prescribed for only 200 out of 7,000 known human diseases, according to Project Remedi’s proposal.

There are few financial incentives to pursue new uses of generic drugs on the list. Even when evidence exists for a new therapeutic use of a particular drug, that knowledge does not rapidly or reliably reach the pharmacists, community health workers and patients who could benefit the most.

For example, N-acetylcysteine, which is on the Essential Medicines List for the treatment of acetaminophen toxicity, has been found to be potentially useful in the treatment of Dengue-associated liver injury. Yet few community health workers know to address this condition with something already available at pharmacies.

“By finding many additional uses and generating substantially higher awareness among targeted practitioners, pharmacists and health workers, we offer a powerful, pragmatic way to affect change,” the proposal states.

WHO is updating its Essential Medicines List and has invited proposals to add to the list. After a lengthy review process, decisions will be announced next summer.

Applicants must prove the efficacy and safety of the drugs they’re recommending through confirmatory clinical trials. And they must be able to disseminate the results to health departments and community health workers throughout the world. All that takes money, which is why Project Remedi entered the 100&Change competition.

Project Remedi’s proposal is bolstered by the expertise provided by the Aurum Institute, a leader in implementing high-impact health care programs and global clinical trials, and the University of Edinburgh’s Global Health Governance Program, which works with governments and other organizations to translate ideas into action.

VUMC’s involvement is key, as it is considered to be the nation’s largest academic generic drug repurposing group, largely because of its unique approach to finding new uses for existing drugs.

BioVU, the Medical Center’s massive DNA databank, enables researchers to look for genetic variations associated with biological changes that are similar to drug effects.

VUMC also is a leader in PheWAS (Phenome-Wide Association Studies), which scan the electronic medical records of thousands of patients looking for associations between genetic variations, diseases and responses to medications.

Combining these methods allows researchers to identify drugs that, by mimicking the beneficial effects of certain genetic variations, may be useful in treating more than one disease or condition.

Regardless of the ultimate outcome of the WHO review, VUMC is committed to impacting global health through drug repurposing, Pulley said.

VUMC’s Drug Repurposing Program was established in 2016 under the Vanderbilt Institute for Clinical and Translational Research (VICTR), which Bernard directs, and is supported by VUMC’s multi-million-dollar Clinical and Translational Science Award from the National Institutes of Health.

“I’ve been doing drug repurposing all my life at Vanderbilt,” said Bernard, an intensive care physician and Melinda Owen Bass Professor of Medicine, who joined the Vanderbilt faculty in 1981.

“Almost every drug I’ve tested in the ICU for sepsis and ARDS (adult respiratory distress syndrome) was an existing drug approved for something else,” he said.

“With the translational science mission plus the assets we have, we should be the ones pursuing generic drug repurposing on behalf of the country if not the world,” Pulley concluded. “Who else is going to be incentivized to do it? Who better than us to be able to do something like that?”

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