Sadly, a major part of the answer to why drugs are so expensive appears to be “because they can be.”

But the high cost of drugs has also spurred a number of attempts to find medicines that are innovative but remain affordable.

Drug repurposing, or using a drug that has been developed for one ailment to treat a different one, is one such strategy. The scientific literature is dotted with papers describing individual drugs that are approved in one indication and useful in another.

Recently, researchers at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT reported on the largest such project to date. By screening more than 4,500 drugs, roughly three-quarters of which were either approved agents or in clinical trials, against nearly 600 cancer cell lines, the team identified roughly 50 drugs that could selectively kill cancer cells.

Steven Corsello, Dana-Farber Cancer Institute

Collectively, the project identified “completely unexpected starting points for therapeutic projects,” Steven Corsello told BioWorld, and demonstrated that “non-oncology drugs can be used to find new ways to treat cancer.”

Corsello, an oncologist at the Dana-Farber Cancer Institute and a researcher at the Broad Institute, is the first author of the paper describing the findings, which was published online by Nature Cancer on Jan. 20, 2020.

He is also the founder of the Broad’s Drug Repurposing Hub, which includes a curated open-access library of currently more than 6,000 compounds and more than 2,200 protein targets.

The project itself is not primarily concerned with addressing drug pricing, Corsello said, but by the idea that “we should maximize whatever has already been discovered and can be brought to patients quickly.”

Still, one potential advantage of drug repurposing is that older drugs, though they, too, can skyrocket in price, are on the average cheaper than newer ones.

The key to scaling up the repurposing project, Corsello explained, was the use of a molecular barcoding technology that introduced a unique DNA sequence into each cell line.

The barcodes allow researchers to pool cell lines when testing them against therapeutics, which “dramatically accelerates” the ability to screen multiple cell lines.

Corsello said that it is “too early to say for sure which of [the drugs] has the most clinical potential.”

Broadly speaking, there are two ways in which drugs identified in this or other repurposing studies could reach that potential.

“For drugs that are already available in inexpensive generic forms, maybe the best way is to do a trial,” Corsello said, whereas for drugs that are working via a different mechanism in cancer than in their approved indication, “it could be advantageous to tweak the chemical structure” for both safety and efficacy purposes.

The work, Vikas Sukhatme told BioWorld, is “a wonderful use of a number of technologies to figure out how non-oncology drugs might be brought to bear on cancer.”

Sukhatme, who was not involved in the Nature Cancer study, is the dean of Emory University School of Medicine, and director of the Morningside Center for Innovative and Affordable Medicine, which is attempting to tackle repurposing on the clinical end.

The short-term goal of the center is to start three to six clinical trials over the next few months to test repurposed drugs.

Putting drugs through the clinical trial process would address one stumbling block for repurposing – that payers are often reluctant to reimburse for off-label use of drugs, regardless of whether the off-label treatment is cheaper than approved options.

Researchers at the Morningside Center, he said, are “also spending a lot of time trying to make sense of this data – why does metformin have some activity, why do beta-blockers have some activity” in cancer patients.

Sukhatme said that a “surprising and rather important” lesson from the work reported in Nature Cancer by Corsello and his team was that “the pattern of killing correlated with the drug’s intended target” in fewer than 1% of the compounds the team identified as having anticancer activity.

The fact that most of the compounds were working via off-target effects, he said, suggests that by optimizing the drugs for the anticancer target, their activity could be further improved.

That, in turn, “could encourage pharma to get into” repurposing efforts.

From a scientific perspective, the results are “sobering at the same time – it means there’s a lot we don’t know about drugs that are out there, when it comes to repurposing,” Sukhatme said.

“Having a paper like this is a first step – a very important first step” to identifying repurposing candidates, Sukhatme said.

The Morningside Center, however, is taking a different tack to identifying the candidates it wants to test clinically.

“We will not de novo look for new drugs to repurpose,” Sukhatme said. Instead, the Morningside Center finds drugs that appear to improve outcomes when they are used by patients by looking at epidemiological data.

“Our goal is to run studies that are heavily biomarker informed,” Sukhatme said, “and give an efficacy signal as quickly as possible, with acceptable toxicity.”

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