Freakonomics Radio

664. Are Thousands of Medical Cures Hiding in Plain Sight?

February 20, 2026

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  • Existing FDA-approved drugs, often generic, represent a vast, untapped resource for treating rare or neglected diseases, as demonstrated by the successful repurposing of nitroxyline for Balamuthia and rapamycin for Castleman disease. 
  • The primary obstacle to drug repurposing is a broken economic system where the low cost of finding new uses (about 1% of new drug development) is matched by zero financial upside for companies, especially for generic drugs, leading to a lack of incentive for necessary clinical trials. 
  • Innovative economic mechanisms, such as Advanced Market Commitments (pull funding) proposed by the Market Shaping Accelerator, are being developed to create financial incentives for companies to invest in proving the efficacy of existing drugs for new indications, ensuring the government only pays upon demonstrated success. 

Segments

Balamuthia Treatment Example
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(00:01:03)
  • Key Takeaway: The drug nitroxyline, approved in Europe for UTIs, successfully treated a patient with the rare, deadly brain-eating amoeba Balamuthia after an emergency IND was granted by the FDA.
  • Summary: Balamuthia is an extremely rare, often fatal brain-eating amoeba infection lacking FDA-approved treatments. A clinician used nitroxyline, an existing European UTI drug, based on pre-clinical amoebicidal activity data. This case highlights how existing drugs can offer life-saving options for diseases with high fatality rates.
David Fajgenbaum’s Origin Story
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(00:04:02)
  • Key Takeaway: David Fajgenbaum’s career pivot to medicine was catalyzed by his mother’s brain cancer diagnosis, leading him to dedicate his life to finding treatments for diseases lacking them.
  • Summary: Fajgenbaum initially focused intensely on becoming a college quarterback before his mother’s diagnosis shifted his focus to medicine. He later faced a near-fatal relapse of Castleman disease, a rare condition with no approved drugs at the time. This personal crisis motivated him to seek existing medicines for repurposing rather than waiting for new drug development.
Finding a Cure for Castleman Disease
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(00:09:58)
  • Key Takeaway: Fajgenbaum used systematic literature review and community building, culminating in the discovery that the mTOR pathway was overactive, leading to the successful repurposing of rapamycin (Sirolimus).
  • Summary: Fajgenbaum initiated his search by emailing thousands of authors linked to Castleman disease literature and hosting an expert meeting to build a research community. He analyzed his own stored blood samples using serum proteomics, identifying an overactive mTOR pathway signature. This data pointed toward existing mTOR inhibitors, like rapamycin, which had been discovered randomly from soil samples on Easter Island decades earlier.
Every Cure’s AI Repurposing Platform
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(00:17:57)
  • Key Takeaway: Every Cure uses AI and biomedical knowledge graphs to systematically score the likelihood of all 4,000 known drugs treating all 18,000 diseases, focusing human effort on the highest probability matches.
  • Summary: Inspired by his success, Fajgenbaum launched Every Cure to scale drug repurposing efforts beyond his lab’s initial 14 discoveries. The platform maps biomedical concepts and relationships to generate scores for potential drug-disease matches. This AI approach acts as a ’low-hanging fruit finder,’ directing medical teams toward promising, already-approved substances like lidocaine for breast cancer.
Economic Barrier to Generic Repurposing
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(00:22:54)
  • Key Takeaway: While repurposing generic drugs is scientifically easier and cheaper, the lack of patent protection and market exclusivity removes any financial incentive for companies to conduct the necessary clinical trials.
  • Summary: The economic incentives for developing new drugs are strong, but they vanish when a drug goes off-patent, even if a new, high-impact use is found. Existing laws allowing patents on new uses are unenforceable because doctors prescribe the generic version, not the patented use. This results in a situation where potentially life-saving research is neglected because no entity profits from it.
Market Shaping Accelerator’s Pull Funding
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(00:27:20)
  • Key Takeaway: The Market Shaping Accelerator (MSA) advocates for ‘pull funding’ mechanisms, like Advanced Market Commitments, where governments promise a reward based on a drug’s proven impact, thereby incentivizing companies to conduct repurposing research.
  • Summary: The MSA, co-founded by Chris Snyder, uses pull funding—a commitment to buy a product that doesn’t exist yet—to stimulate research, contrasting with ‘push funding’ that supports inventors early on. A successful $1.5 billion Advanced Market Commitment for a pneumococcal vaccine demonstrated this model’s power, credited with saving 700,000 children’s lives. Their current proposal suggests the US government could offer rewards based on projected savings (e.g., $2,000 per patient) to incentivize generic drug repurposing.
FDA Perspective on Repurposing Data
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(00:43:33)
  • Key Takeaway: Heather Stone notes that adoption of new medical advancements, especially those lacking commercial marketing, averages 17 years, and while CureID generates valuable hypotheses, it is not designed to replace rigorous, randomized FDA approval trials.
  • Summary: Heather Stone, an FDA analyst, highlights the slow adoption rate for new medical advancements when commercial incentives are absent. She personally benefited from Lyrica, repurposed for fibromyalgia, illustrating the value of these findings. CureID, a treatment registry, collects real-world data to generate hypotheses for future robust studies, but the FDA requires more formal evidence for approval.