Sustainable approaches for drug repurposing in rare diseases: recommendations from the IRDiRC Task Force

Abstract

Drug repurposing represents a real opportunity to address unmet needs and improve the lives of rare disease patients. It is often presented as a faster, safer and cheaper path for bringing drugs into new indications. However, several economic, regulatory and scientific barriers can impede the successful repurposing of drugs for rare diseases. The International Rare Diseases Research Consortium (IRDiRC) set up the Task Force on Sustainable Models in Drug Repurposing with the objective of identifying key factors for achieving sustainable repurposing approaches in rare diseases. In order to help inform expert opinion, the Task Force investigated six cases of medicinal products repurposed into new rare indications and four cases of ongoing development programs. A questionnaire addressing the major steps of the repurposing approach was developed by the Task Force and sent to contact points of the organizations. In addition, interviews were conducted with the relevant organization representatives to conduct a deeper dive into the sustainability of the repurposing approach for each of the selected cases. Based on the collective experience of the members of the Task Force and the output from the questionnaires/interviews, we have identified ten key factors that should be considered by those embarking on repurposing projects. These factors include the identification of unmet patient needs and partnership with patients, collection of evidence concerning disease prevalence, patient numbers, drug pharmacology and disease etiology, drug industrial property status, off-label or compounding use, data from past clinical studies and needs for extended non-clinical and clinical studies. The development of a collaborative funding framework and early discussion with regulators and payers are additional factors to implement early in the development of sustainable drug repurposing projects.

International regulatory and publicly-funded initiatives to advance drug repurposing

“…This could offer opportunities for collaboration and harmonization and confirms the progress the repurposing ecosystem has experienced since its inception. The knowledge gap in regulatory expertise for non-traditional repurposing programs is being addressed by initiatives like STARS and the IRDiRC Task Force but remains a challenge (17,22,23). In limited cases regulators are incentivizing industry to update labels using existing mechanisms within their regulatory framework.…”

New clinical insight in amyotrophic lateral sclerosis and innovative clinical development from the non-profit repurposing trial of the old drug guanabenz

“…This may be due to expiring intellectual property rights or lack of incentives that make the burden of going through the necessary development unattractive to industry, particularly if the target is a rare or ultra-rare disease. As a result, clinical development using this approach is more frequently attempted by academics, often together with non-profit organizations ( 40 , 41 ), seeking an opportunity to test a therapeutic approach for an orphan disease, also taking advantage of similarities with other disorders ( 42 ). Although it is easier to do this with a drug already on the market, there are still many barriers to clinical development.…”

Drug repurposing for rare: progress and opportunities for the rare disease community

“…It explores incentives, regulatory tools, initiatives, and development tools for drug repurposing, helping developers ask the right questions at the right time ( 8 ). Previously, other IRDiRC endeavors have investigated key features of successful, innovative drug repurposing projects, and the corresponding business and funding models ( 9 ). As such ten factors were found to significantly contribute to the outcomes of repurposing projects.…”