While drug repurposing is generally faster and cheaper than drug development ‘from scratch’, we face numerous challenges along the way, including low financial incentives for companies and suboptimal legislation for adding new indications to existing drug labels.
In this article, we talk to the Anticancer Fund, a Brussels-based non-profit organization that works with universities, hospitals, and researchers to investigate new cancer treatments and provides personalized support for cancer patients with science-based information, to see where the field is and where it’s heading.
A ready-made launch pad for new treatments
The advantages of repurposing existing drugs are clear. When a regulatory agency grants approval of a drug for a particular disease, we know the drug is functional and safe in humans. These two factors mean a potentially quicker and cheaper route to the clinic if the drug is also found to have beneficial effects for other diseases.
“One of the main advantages of drug repurposing is that the tools already exist. You don’t need to create them. You can use them immediately, which is a big strength,” says Dr. Gauthier Bouche, director of clinical research at the Anticancer Fund, a pioneer in drug repurposing that has established clinical trials mainly focused on repurposing existing drugs to treat cancer. “You know the drugs are safe and how they should be administered to patients. This allows you to save time when you want to treat a new patient population if you have a strong scientific rationale for doing so. This also makes it much faster in terms of regulatory approval and speeds up access for patients who need treatments.”
While it’s gaining popularity, the repurposing of approved, shelved, or discontinued drugs is not a new idea. Between 1984 and 2009, 35% of transformative drugs approved by the Food and Drug Administration (FDA) were repurposed from other indications, with most approved before 2000.
The Anticancer Fund’s database of active clinical trials investigating the use of non-cancer drugs as potential cancer treatments currently lists 911 active trials, with 161601 patients planned for inclusion across 44 countries, highlighting the extensive interest in drug repurposing. Over 15% of these trials are in phase 3 or 4, meaning real-world benefits for thousands of cancer patients may be just around the corner.
A game of chance?
Historically, some drug repurposing success stories arose by chance, thanks to the discovery of beneficial side effects of existing drugs or drugs that failed for their primary indication. For instance, the drug company Pfizer initially trialed the erectile disfunction drug, Viagra, in a phase 1 clinical trial to treat angina. While the drug failed to treat angina, male trial participants reported unforeseen (but beneficial) side effects. Pfizer rescued the drug and it became a blockbuster, even undergoing subsequent repurposing to treat the serious lung condition, pulmonary arterial hypertension.
Another serendipitous drug repurposing was for the use of a beta-blocker called propranolol to treat benign vascular tumors called hemangiomas in infants. Infantile hemangiomas appear in around 10% of children within the first few weeks after birth, but while most shrink naturally, some grow aggressively, leading to debilitating symptoms. Propranolol was developed in the 1960s to treat heart conditions, however in 2007 a French pediatric dermatologist treating an infant with a heart condition and severe hemangioma made the chance observation that the hemangioma shrank dramatically after taking propranolol. Subsequent clinical trials led to the FDA approval of a propranolol formulation specifically for infantile hemangiomas in 2014. It is the first and only treatment for this disorder.
“In this case, it’s a win-win in the sense that it’s good for the patients but also for the company. By improving the product for administration in infants, the company actually did what they are supposed to do. I think it’s a really interesting and successful story,” says Dr. Bouche.
Trouble in the pipeline
Despite this success story, some companies are often not interested in the additional expensive research and regulatory hurdles necessary to approve a new indication for their existing drugs despite potentially quicker development pipelines. This is especially true when these drugs are already cheap or off-patent, where the financial reward of repurposing the drug for another indication is minimal.
“One problem is that the financial model is largely ineffective. This means there’s not a lot of private investment going to the development for new indications because there’s no monetary reward at the end,” emphasizes Dr. Bouche. “That’s where not-for-profit organizations like the Anticancer Fund or government funds are really needed to repurpose promising drugs which are cheap or off-patent.”
Even if investment is found and independent clinical trials are successful, the responsibility for getting approval and adding new indications to an existing label rests with the company that developed the drug. This can be problematic as the process takes both time and money to be successful. “The original drug manufacturer is not obliged to add new indications to the label. The system does not currently allow someone else to do it for them,” explains Dr. Bouche.
The Anticancer Fund and others are pushing for a change in European Union legislation to make it easier for not-for-profit organizations to submit clinical data for a new therapeutic indication to the regulatory authorities. Article 48 currently deals with this issue. “The idea is to open the possibility for a third party to submit data to the European Medicines Agency, who will look into it and decide whether the new indication should be added to the label or not, regardless of what the company wants,” says Dr. Bouche.
If the legislation passes without amendments, it might incentivize more clinical research into repurposing and streamline the route to patient access, however dialogue with pharmaceutical companies that own the drugs is crucial.
The future is bright
Another potential turning point in drug repurposing pipelines is that of big data analytics and artificial intelligence (AI). But how much impact will this have on the future of drug repurposing?
“The future is bright as I think AI opens up even more opportunities,” emphasizes Dr. Bouche. “One of the challenges in tackling a specific disease is to identify the right targets and the right drugs. I think AI is going to help us identify targets for diseases where we have no clue what’s going on at the cellular level, and also then to match them to some given drugs.”
New AI models can identify therapeutic candidates even for diseases where no drugs or other treatment options exist. For instance, the drug repurposing AI model TxGNN ranks drugs with potential indications and contraindications for over 17,000 diseases. The researchers found that new predictions aligned well with off-label prescriptions previously made by clinicians, potentially speeding up the route to the clinic.
Despite this optimism, Dr. Bouche remains cautious, owing to the complexity of the biological validations required to confirm any predicted drug-disease indications from AI.
“Biological validation is the hard part and many predictions won’t work out due to the biological complexity involved. So, I’m not sure AI is going to increase or improve the success rate, but I think it will give more opportunities, especially where there’s little to no information to start with.”
