Unlocking Hidden Cures: The Economics and Science of Drug Repurposing

This episode of Freakonomics Radio, guest-hosted by Steve Levit, delves into the profound potential and economic challenges of drug repurposing—finding new uses for existing, approved medications. It opens with the story of Balamuthia, a rare brain-eating amoeba, where an old European UTI drug, nitroxoline, remarkably saved two patients, highlighting that many diseases lack approved treatments despite existing drugs. The narrative then pivots to Dr. David Fagenbomb, a physician-scientist whose personal battle with the rare and deadly Castleman disease became the catalyst for his groundbreaking work. After multiple near-fatal relapses and exhausting conventional options, Fagenbomb embarked on a desperate, self-driven quest to understand his disease and find a cure, inspired by the fact that the chemotherapies he received were not originally for Castleman's. Fagenbomb's meticulous self-experimentation, involving collecting and analyzing his own blood and lymph node samples, led to the novel discovery that the mTor pathway was in overdrive in his immune system. This insight allowed him to identify sirolimus (rapamycin), an FDA-approved mTor inhibitor originally discovered in Easter Island soil and used for organ transplant rejection, as a potential treatment. This drug, which was almost discarded by its original developers, ultimately saved his life and subsequently helped several other Castleman disease patients, demonstrating the serendipitous and often non-linear nature of drug discovery. This personal triumph underscored the vast, untapped potential of existing drugs. Inspired by his survival, Fagenbomb co-founded Every Cure, an organization dedicated to systematically identifying and validating new uses for all 4,000 existing drugs against all 18,000 known diseases. Their approach leverages AI and biomedical knowledge graphs to quantify the likelihood of a drug-disease match, sifting through millions of potential connections to find high-probability candidates. A compelling example is lidocaine, a common numbing agent, which a large clinical trial showed could reduce breast cancer mortality by 29% when injected around tumors before surgery. Despite this significant finding, the practice is not widespread, primarily due to the lack of financial incentives for generic drug manufacturers to promote or further research new applications. The core economic problem lies in the fact that while repurposing drugs is significantly cheaper and faster than developing new ones (about 1% of the cost), there is virtually no financial upside for pharmaceutical companies, especially for generic drugs. This market failure creates a massive missed opportunity for public health. The episode concludes by exploring potential solutions, such as Advanced Market Commitments (AMCs), a mechanism developed by economists Rachel Glenner and Michael Kramer. AMCs, like the one used for the pneumococcal vaccine, offer guaranteed payouts for successful development of desired products, thereby creating market incentives where none previously existed, and encouraging innovation for public good without relying solely on traditional profit motives.

There are 18,000 known human diseases, but only about a quarter of them have an FDA approved treatment.

How many more things are there that we could potentially uncover to save lives today? Cuz these drugs are already at the pharmacy. They're already manufactured. They're already available.

I realized that if I wanted any chance to survive, I would have to really turn my hope into action and start trying to find a drug that could save me.

What I thought was possible was maybe I could find an old drug for another disease that could save me.

MTOR actually stands for mamalian target of rapamy. like this thing in our body is inhibited so well by this drug rapamy that we named the thing after the drug.

It cost about 1% of the cost to develop a new drug, to repurpose a drug and find a new use for an old drug. And of course, the economic reason is that though it's much, much, much less expensive to do it, there is zero financial upside.

The patients who were randomly assigned to have the injection around their tumor had a 29% reduction in mortality. This is startling because a 29% reduction in mortality is a huge mortality improvement.

You dangle market incentives and the right parties who are going to actually have the best ideas will in a sense self-organize just as markets often do and bring themselves through the pipeline to try to get that reward at the end.