Cambridge study of FDA files puts drug ‘repurposing’ in perspective
Drug ‘repurposing’ has enjoyed some high-profile wins, such as Viagra, but a new study at Cambridge Judge Business School shows how tough it is to find entirely new uses for existing molecules.
The repurposing of existing drugs can be valuable but the Judge study found that only two per cent of new molecules entering clinical trials were ultimately launched in an area other than the one they were initially tested in.
The study published in the journal Drug Discovery Today is based on US Food and Drug Administration approvals and the full clinical development history of more than 800 new molecular entities over a 32-year period.
The study cautioned against relying too much on the “excitement” that has surrounded some high-profile repurposing successes – most famously the development of the erectile-dysfunction drug Viagra from a failed drug designed to treat angina (chest pain from reduced blood flow to heart muscles).
Most repurposing attempts and successes have come in the same therapeutic area as originally tested, the study found, which is “outside of the main theme of repurposing, that of finding entirely new uses for existing molecules.”
The study noted that there had been “compelling stories” by repurposing advocates, along with some estimates of repurposing success rates ranging from 30 per cent to 75 per cent – but no data to support such projections. So the researchers examined 834 drug candidates that started clinical trials between 1980 and 2012, and found that repurposing “successes are unlikely to occur” at such high estimated rates.
“Turning base metal into gold has been difficult for a long time, and repurposing is unlikely to fill our future medicine cabinets singlehandedly,” the paper concludes, so research to discover new compounds is essential despite “inexorably increasing” new drug development costs.
Study co-author, Nektarios Oraiopoulos, of Cambridge Judge Business School, said: “We felt it was important to look at a more extensive dataset than the handful of success stories that surround drug repurposing.
“Attempting to repurpose some drugs can be a good approach given the rising costs of new drug development but the data shows a low overall success rate for repurposing – particularly in producing successes in a new disease setting.”
The study – ‘Renovation as innovation: is repurposing the future of drug discovery research?’ – was co-authored by Arthur Neuberger, PhD candidate in pharmacology and biochemistry at the University of Cambridge; Nektarios Oraiopoulos, University Lecturer at Cambridge Judge Business School; and Donald Drakeman, Fellow in Health Management at Cambridge Judge Business School.
The study found that drug companies attempted to expand use in the same therapeutic area (for example, testing a breast cancer drug for ovarian cancer) for 31 per cent of products approved by the FDA, and those extensions had a high success rate of 67 per cent.
Those percentages drop significantly in seeking to repurpose successful drugs in different therapeutic areas: 18 per cent of products were tried in another area, with a 33 per cent success rate.
“The alchemy involved in turning failures into successes is even more complicated,” the study found. “Only 16 per cent were tried in another indication, and most were in the same therapeutic area, with only 10 per cent of the initial failures tried in a different area altogether.”
The success rate was just nine per cent whether the therapeutic areas were the same or different.
Yet the study points out that “rewards can be substantial” for this type of failed-to-successful repurposing: infliximab and etanercept, both initially developed for treating sepsis (overreaction of the immune system to infection or injury), were later approved to treat rheumatoid arthritis and are now among the world’s 10 top-selling drugs.
There were no predictive patterns among successfully repurposed products – with similar success rates for small and large molecules, and successes distributed across a wide range of therapeutic areas.
Overall, the study found: “Of the 834 new molecules entering clinical trials, less than two per cent were ultimately launched in a therapeutic area other than the one in which they were originally tested.
“Most new medicines were the products of de novo discovery that succeeded in the originally expected therapeutic area.”
The study concludes that for products resulting from large amounts of time and resources in research, development, testing and manufacturing, “there can be good reasons to consider the possibility of repurposing, even after an initial clinical failure.”
Yet, “as promising as repurposing might be, basic research remains essential. It will not only help us understand where failed drugs might have a second chance, but, more importantly, will also continue to create a fertile environment for the often-unexpected discoveries that can launch entirely new classes of medicine.”
• PHOTOGRAPH SHOWS: Nektarios Oraiopoulos, University Lecturer at Cambridge Judge Business School