Drug Repurposing as an Innovative Strategy in Drug Development
Drug repurposing is an innovative approach to drug development.
Instead of developing an entirely new compound to target a particular biological mechanism or protein, Drug repurposing takes advantage of what is already known about the targets and Mechanism of action of drugs that are already in use.
A single molecule can have multiple uses e.g. Everolimus, a drug originally indicated for use in preventing rejection in organ transplantation, is now used for multiple benign and cancerous tumours, the Rare disease tuberous sclerosis complex (TSC), and seizure Prophylaxis .
What’s an example of a multi-disease approach?
Repurposing for Niemann-Pick Type C
What is Niemann-Pick Type C?
Niemann-Pick Type C (NPC) is a rare lysosomal storage disease caused by inherited mutations in the NPC1 or NPC2 genes. These mutations lead to the accumulation of large molecules such as cholesterol and lipids in cells, ultimately damaging the brain, liver, and spleen. Symptoms of NPC usually appear in childhood and can include jaundice, an enlarged liver, ataxia (uncoordinated movement), cognitive difficulties, and progressive neurological decline, which is ultimately fatal.
What is N-acetyl-DL-leucine?
N-acetyl-DL-leucine is a generic compound that has long been used to treat vertigo. A small US biotech company, IntraBio, began investigating this molecule as a potential treatment for a range of neurodegenerative diseases, including NPC. Through this work, IntraBio identified the active component of the compound (IB1001), which led to the initiation of formal clinical trials in NPC patients. In June 2023, results from a Phase III clinical trial showed that IB1001 reduced neurological signs and symptoms in people with NPC. Following these results, the company began seeking marketing authorisation for IB1001 as a treatment for symptom management in NPC.
What was innovative about the trial design?
A key feature of this development programme is the use of one molecule across multiple indications. By running clinical trials in different conditions using the same drug, the company maximises the likelihood that at least one group of patients will benefit from the research.
The Phase III NPC trial used a cross-over trial design, in which participants received either the drug or a placebo for 12 weeks before switching treatments. This ensured that all participants had the opportunity to receive the active drug. While this design is not suitable for every disease, it worked well in NPC because changes in symptoms such as ataxia can be observed relatively quickly.
We would like to extend our thanks to Will Evans, whose eldest son, Sam, was diagnosed with NPC in 2008. Will has been a trustee of Niemann-Pick UK since 2010 and served as chair of the charity from 2016 to 2022.
If you’d like to see a more detailed PDF version of this case study, please download it below:
Other drug repurposing initiatives
The COVID-19 pandemic has accelerated interest in drug repurposing in recent years. As a result, multiple initiatives on national and global levels, including REMEDi4ALL , have been established or advanced to help continue this engagement and interest and to support those who are pursuing drug repurposing projects. Some of these initiatives can be found below:
- NHS medicines repurposing programme (UK)
- SIMPATHIC
- REPO4EU
- LifeArc
- NCATS New Therapeutic Uses (US)
- C-Path CURE ID (US)
- MHRA Innovative Licensing and Access Pathway (ILAP)
- EMA Safe and Timely Access to Medicine for Patients (STAMP) framework
- EveryCure
What makes drug repurposing innovative?
1. New tools (in silico, AI) making better use of existing data can efficiently generate more sound DR hypotheses that can be tested (in a streamlined platform).
2. An existing product can find wider application in other diseases, increasing impact and exploitation of the current drug.
3. The same active pharmaceutical ingredient (API) compound can end up in multiple (bespoke) Drug products (different Formulations or Dose strengths, tailored to the target population or individual – in the extreme coined as personalised medicine).
4. New Intellectual property (IP) can be generated.
5. Combinations of existing drugs can be more effective (synergistic) where dose of individual drugs can be lowered and Side effects reduced.
6. Timely because certain early development steps (e.g. Safety -toxicity profiling) could be avoided and production/market distribution is already in place.
Learn More
Drug Repurposing: a Nexus of Innovation, Science, and Potential
Short (1000 word) article about DR. Covers speed AI and scope.
Orphan Drug Guide
A patient focused guidebook that describes the available tools, Incentives , resources and practices specific for developing traditional and innovative drugs/therapies for rare disease Indications and how to best use them.
REMEDi4ALL Glossary
The REMEDi4ALL glossary aims to make more accessible the terminology commonly used in drug development including drug repurposing.
Discover New Therapeutic Uses for Existing Drugs
Webinar hosted by UCL’s Repurposing Therapeutic Innovation Network, discussing how a multi-disciplinary approach can be used to drive drug repurposing.