Drug Repurposing: Unlocking Cures Within Existing Pharmaceuticals

This conversation, featuring Dr. David Fajgenbaum and guest host Steve Levitt, uncovers a profound, yet largely overlooked, opportunity to combat disease: the repurposing of existing, FDA-approved drugs. The non-obvious implication is that thousands of potential cures for rare and devastating illnesses might already exist in pharmacies, waiting to be identified. This revelation challenges the conventional, linear path of drug discovery, which is prohibitively expensive and time-consuming. This discussion is crucial for anyone involved in healthcare, research, or policy, offering a strategic advantage by highlighting a more efficient and cost-effective route to saving lives. It reveals a systemic failure in incentivizing the exploration of these existing treatments, suggesting that the true bottleneck isn't scientific innovation, but rather economic and logistical frameworks.

The Hidden Cost of "New" and the Untapped Potential of "Old"

The prevailing narrative in medicine is that innovation means creating something entirely novel. Yet, Dr. David Fajgenbaum, a physician scientist and co-founder of Every Cure, presents a compelling counter-argument rooted in his own near-fatal experience with Castleman disease. He discovered that existing drugs, approved for entirely different conditions, could be life-saving. This isn't a theoretical musing; Fajgenbaum's lab has identified 14 drugs for diseases they weren't intended for, saving over a thousand lives. The core insight here is that the arduous, multi-billion dollar, decade-long process of discovering and approving new drugs often overlooks the vast, already-vetted library of existing pharmaceuticals.

"Once you're dealing with FDA approved drugs you already know how it works in the body because it's been proven you already know that it's safe enough to be approved for one thing and you actually also already know that it can do something in the body that can be clinically meaningful for a particular condition."

The immediate benefit of using an existing drug is clear: reduced development time and cost. However, the downstream consequence of not systematically exploring this avenue is the continued suffering and death from diseases that could be treated. Heather Stone, a policy analyst at the FDA, highlights the case of Balamuthia, a brain-eating amoeba for which no treatments were approved. A clinician successfully used nitazoxanide, a drug approved in Europe for UTIs, demonstrating that "biochemistry can surprise you." This isn't about finding a miracle cure; it's about recognizing that the biochemical properties of drugs often extend beyond their initial approved indications. The system, however, is not geared towards this discovery.

The Broken Incentive Engine: Why "Good" Doesn't Always Mean Profitable

The central tension revealed in this conversation is the misalignment between scientific possibility and economic incentives. While Fajgenbaum's personal journey and the work of Every Cure demonstrate the immense potential of drug repurposing, the economic landscape offers little reward. Chris Snyder, a Dartmouth economist, explains that for branded drugs, companies might pursue new uses if it expands their market. But for generic drugs, once off-patent, the financial incentive to conduct the costly clinical trials for new indications disappears.

"The trouble is that that's true for branded drugs but not for generic drugs once a drug goes off patent essentially any incentive to come up with new uses and to do the clinical trials those incentives drop off a cliff."

This creates a scenario where potentially life-saving discoveries, like lidocaine's observed 29% reduction in mortality for breast cancer patients when injected around tumors before surgery, go unutilized. Why? Because no single company stands to profit from a generic drug that costs pennies per dose. The market shaping accelerator, co-directed by Snyder, aims to address this by proposing "pull funding" mechanisms, like advanced market commitments. This approach promises a reward after a new use is proven, aligning financial incentives with successful outcomes rather than the risky, upfront investment in drug development. The COVID-19 vaccine development, spurred by both push (R&D funding) and pull (purchase commitments) mechanisms, serves as a recent, albeit emergency-driven, testament to this strategy's power.

The 17-Year Delay: From Discovery to Doctor's Prescription

Even when a drug repurposing discovery is made and validated, the journey to widespread clinical adoption is fraught with delays. Heather Stone notes that, on average, it takes 17 years for a new medical advancement to be adopted, a timeline that is likely even longer for repurposed drugs lacking commercial marketing. This is where the Cure ID platform, a treatment registry for repurposed drugs, plays a critical role. It functions as a crowdsourced database, allowing patients, caregivers, and clinicians to share experiences and explore what has worked.

"The idea of pull funding so the idea is if a firm went in and got fda approval for a new indication for a drug that the way they'd become compensated would be after the fact by going in and looking at the data and saying how much good is this drug doing in this new setting."

While Cure ID generates valuable hypotheses and data, its success hinges on voluntary contributions, highlighting another systemic challenge: the lack of incentives for clinicians and patients to log their experiences. The "sexiness" problem, as Stone puts it, is real. Drug repurposing isn't as glamorous as discovering a novel molecule. This is precisely why organizations like Every Cure, which have raised over $100 million, are crucial. They are systematically tackling this neglected area, aiming to treat 15-25 debilitating conditions in the next five years. The implication is that without dedicated organizations and innovative funding models, countless lives remain at risk, not due to a lack of scientific knowledge, but due to a failure in our economic and logistical systems to capitalize on it.

Key Action Items

• Immediate Action (Next 1-3 Months):
  • Explore Cure ID: Clinicians and patients should actively contribute their experiences with repurposed drugs to the Cure ID platform to build a more robust dataset.
  • Internal Knowledge Sharing: Healthcare institutions should establish internal forums for clinicians to share anecdotal successes and challenges with off-label drug use.
  • Educate Yourself: Seek out and listen to the full Freakonomics Radio episode "664. Are Thousands of Medical Cures Hiding in Plain Sight?" to grasp the full scope of the issue.
• Short-Term Investment (Next 3-9 Months):
  • Advocate for Policy: Support organizations and policymakers advocating for government-backed pull funding mechanisms for drug repurposing research.
  • Support Repurposing Organizations: Donate to or otherwise support non-profits like Every Cure that are systematically working on identifying and validating repurposed drugs.
  • Pilot "Low-Hanging Fruit": For institutions with research arms, identify and initiate small-scale observational studies on highly promising, low-cost repurposed drug candidates identified through platforms like Cure ID or Every Cure.
• Long-Term Investment (12-24+ Months):
  • Establish Dedicated Repurposing Funds: Governments and large foundations should create dedicated, substantial funds specifically for advanced market commitments or similar pull incentives for drug repurposing.
  • Integrate Repurposing into R&D: Pharmaceutical companies should establish dedicated internal teams or partnerships focused on systematically identifying and validating new uses for their existing drug portfolios, particularly generics.
  • Systemic Incentive Reform: Develop novel economic models that reward the discovery and validation of new uses for generic drugs, potentially through tax credits, tiered reimbursement, or patent extensions on the use rather than the molecule itself. This requires significant effort now for a payoff that could dramatically reduce healthcare costs and improve patient outcomes over years.