A seemingly small semantic issue is a major roadblock to develop treatments for rare diseases

Finding a new medicine is never easy. But developing treatments for patients with rare diseases — conditions that afflict fewer than 200,000 people in the United States — is particularly challenging.

When there are only a few thousand or even a few hundred people living with a particular condition, finding enough patients for clinical trials can take years. Clinical trials also typically require collaboration between multiple academic health centers, and care is often not standardized due to disagreements among researchers about what a “successful” drug should do. Many biotech companies also shy away from rare disease research, since the potential financial returns can be comparatively low, given the small population of potential customers.

Fortunately, the FDA recognizes the need to speed up rare disease research. In 2022, the agency’s Center for Drug Evaluation and Research launched the Accelerating Rare Disease Cures Program.

Though the program is well-intentioned and welcome, it would benefit from a seemingly minor but hugely important clarification. Namely, officials ought to distinguish between “repurposing” FDA-approved drugs for new indications vs “repositioning” non-FDA approved shelved assets for emerging indications.

Drug repurposing is a decades-old practice. Aspirin, at first a painkiller, is now also used to prevent blood clots. Amantadine, originally developed for influenza, was later repurposed as a therapy for Parkinson’s disease. During the pandemic, many drugs — including baricitinib, remdesivir, and tocilizumab — that were originally designed to treat other diseases were repurposed as potential Covid-19 treatments.

Repositioning drugs, by contrast, entails taking a second look at experimental therapies that were designed to treat a specific condition but have been “shelved” by their developers for a variety of reasons. A shelved asset is often seen as a commercial failure, so for a biotech company to spin off the drug or put more resources into its development, many internal champions are needed — especially since bringing shelved assets to market can still require shelling out billions of dollars and taking on massive amounts of risk.

But these quick definitions aren’t even universally agreed upon. In fact, “repurposing” and “repositioning” are often used interchangeably, or used to mean different things by different organizations. A study by researchers at Utrecht University found that among articles that used the terms “drug repositioning,” “drug repurposing,” or similar vocabulary, less than one-third even included definitions.

For pharmaceutical companies, universities, and research organizations to cooperate efficiently, they need to agree on definitions. And right now, there are no clear FDA guidelines on the difference between “drug repositioning” and “drug repurposing.” As a consequence, researchers struggle to find willing partners, and opportunities for collaboration proceed more slowly than necessary, if they happen at all.

Repurposed and repositioned drugs involve different reimbursement strategies and commercial value. Repositioned drugs are harder to obtain from pharmaceutical companies — harder to get off the shelf and into the public domain, as it were — but have higher commercial value than repurposed drugs. Convincing pharmaceutical companies to share shelved drug data is a lot easier if everyone agrees on a specific term for the venture. As a study from the Journal of Market Access & Health Policy suggests, it’s impossible to consider the “added value” of repositioned drugs without defining them.

But the value is there. Consider the MEK inhibitor mirdametinib. Pfizer developed the compound to treat cancer but discontinued development for strategic commercial reasons. My organization, the Children’s Tumor Foundation, is laser-focused on accelerating the development of treatments for patients who suffer from neurofibromatosis and schwannomatosis — rare diseases that cause tumors to grow on nerves throughout the body, leading to disabling pain, disfigurement, deafness, blindness, and cancer. After studying Phase 1 and Phase 2 data, we saw the value in mirdametinib. A very fruitful collaboration between the Pfizer chief medical officer, the head of FasterCures, and our team resulted in the spin-out of mirdametinib into a new biotech company, SpringWorks, which launched in 2017.

The Children’s Tumor Foundation has identified many such drug repositioning opportunities that could benefit patients with neurofibromatosis and schwannomatosis. Following the SpringWorks success, we built the BRIDGE Initiative, a partnership between the Children’s Tumor Foundation, CureSearch, and the Milken Institute’s FasterCures.

Yet the initiative’s attempts to match potential new drug developers with shelved compounds encountered a knowledge gap. Due to the confusing terminology surrounding shelved drugs, pharmaceutical companies were hesitant to dole out the resources and share the information needed for successful repositionings.

I propose that “drug repositioning” refer only to non-FDA-approved compounds that could be developed to treat a disease other than the one for which they were originally intended. “Drug repurposing,” meanwhile, should refer to applying already-approved drugs to new diseases.

Better distinguishing between repurposing drugs and repositioning them might sound like a pedantic, purely semantic difference. But it’s not. Clarifying the distinction will help accelerate the development of cures for the rare diseases that collectively afflict 30 million Americans.

Annette Bakker is president of the Children’s Tumor Foundation.