Journalists from New Zealand and Belgium recently interviewed us about our views on drug repurposing: how can existing drugs be used against other diseases, such as cancer? Innovative cancer therapies are extremely expensive and therefore there’s a real need for alternative and cheaper cancer treatments, can repurposing make this possible?

What is repurposing?

Drug repurposing is the re-use of a medicine that was developed for one disease and is later found to be useful for other diseases, such as cancer. Research reveals that the drug can be administered for more diseases than initially thought.

Viagra, or sildenafil, is one of the best known examples. The pharmaceutical giant Pfizer developed the drug in the 1990s to treat hypertension and angina, but during clinical studies it became clear that it could treat erectile problems in men, a condition that had no standard medical treatment at the time.

Another example is Softenon, or thalidomide, which was used in the 60s and 70s as a sleeping pill and as a treatment for morning sickness during pregnancy, but it fell into disuse because it was responsible for serious abnormalities in newborns. Now, almost 50 years later, thalidomide is part of the standard treatment for multiple myeloma, a form of blood cancer.

A huge advantage of drug repurposing is that these drugs are already in clinical use and known to be safe, unlike new medicines which must undergo years of testing to show safety. In principle these repurposed drugs should also be cheap and widely available, another important advantage when developing them for a cancer or any other new disease area. In theory it means that repurposed drugs could get to cancer patients much sooner than newly developed and untested drugs.

Repurposed medicines have an important economic and scientific added value in the longer term. They may reduce the costs of health care and contribute to a more sustainable society. The idea of using an existing medicine for another disease is sometimes based on a chance observation during treatment – for example it has been shown that patients with breast cancer and also treated for high blood pressure with the beta blocker propranolol have better outcomes than similar patients treated with other drugs. In other cases the idea for repurposing comes from basic scientific research into the biology of cancer. But as doctors and scientists are gaining more and more knowledge about diseases and their mechanisms of action, these other applications for medicines are becoming increasingly apparent.

Repurposing in cancer

The Anticancer Fund has drawn up a list of 292 medicines with potential anti-cancer effects. Those drugs, from aspirin to statins, have been mentioned in scientific studies for their potential impact on cancer. Additional clinical research is needed to properly assess the anticancer activity of these drugs in patients.

The 292 drugs can fight cancer in various ways. By influencing the microenvironment of the cancer, for example. Such as slowing down the blood circulation in the blood vessels that stimulate the growth of cancer cells. The focus on at that micro-environment gives standard treatment, such as chemotherapy, a greater chance of success.

CUSP9: the ultimate repurposing study in cancer?

Glioblastoma multiforme (GBM) is the most common brain tumor and a very aggressive form of cancer. Only 5 to 20 percent of patients survive 5 years after the first treatment. Current therapy consists of surgery, radiation and chemotherapy. New, experimental treatments have been failing for decades. The Anticancer Fund has helped to set up a study in which nine existing medicines are administered together to patients with GBM. The idea is that the nine medicines will attack the brain tumor from various angles at the same time.

In 2013, researchers Marc-Eric Halatsch and Richard Kast suggested that the repeated failures of new treatments are due to the ability of glioblastoma to escape the effect of a therapy. More recently the scientists have identified a series of mechanisms that cause tumor growth. The drugs that can act on these mechanisms are now being used to bring the tumor to silence.

The researchers selected 9 drugs to undermine glioblastoma. Hence CUSP9, or Coordinated Undermining or Survival Paths active in glioblastoma by 9 repurposed drugs. The 9 reused medicines are (with their current main indication in brackets): Aprepitant (nausea and vomiting), Minocycline (bacterial infections), Auranofin (rheumatoid arthritis), Disulfiram (alcohol addiction), Ritonavir (HIV), Itraconazole (fungal infections), Captopril (hypertension), Sertraline (depression) and Celecoxib (inflammation).

The phase 1 study, which assessed the safety and provisional efficacy of the treatment, had very encouraging results. Treatment was safe in the 10 patients enrolled in the study and in 5 out of 10 patients, the tumor didn’t progress for more than 12 months. We are working on a phase 2 study to confirm these promising results.

An independent group of researchers from Norway already conducted in vitro experiments with the CUSP9 drugs and published the results. Their findings confirmed the biological rationale of the approach.

We’re almost there

Since several repurposing projects are currently in clinical research stages, it is important to explore how these drugs will eventually be made available to patients, once they are proven effective in clinical studies. Prior to market launch, any drug needs approval, supported by adequate clinical research. Adding a new use to an existing drug (a so called “additional indication” or “label extension”) is possible, if applied for by either the original marketing authorization holder or a generic manufacturer. Sadly, the commercial return of generic repurposing for authorization holders is often too low, which is why this development pathway is rarely pursued. As a result, drugs are often used “off-label”: used for an indication that is not “on the label”.

Most people now agree that this off-label use has important disadvantages, like legal liability issues, reimbursement problems, data collection limitations, and serious supply issues, and should therefore be limited.

To address this issue, the Anticancer Fund has been participating in a multidisciplinary working group of the European Commission expert group on Safe and Timely Access to Medicines for Patients (STAMP) to develop a repurposing pathway that could facilitate bringing new indications on label. This working group has now developed a framework to support not-for-profit organizations and academic institutions in drug repurposing. The proposal is mostly focused on the provision of scientific advice by regulatory agencies to make sure that academic-driven projects fulfill regulatory requirements for marketing authorization. The final framework proposal will be published by the European Commission at the end of July. The next step is to test this framework in a pilot project using concrete examples.

• Our colleague Pan Pantziarka, program- Director of Drug Repurposing of The Anticancer Fund gave a presentation on this topic at an International Symposium on Immunotherapy in May.
• Our Manifesto that we published before the European parliamentary elections also calls for action. Remove barriers to drug repurposing.
• The Anticancer Fund has also been invited in the US to attend a conference and talk about the topic in fall. Proof that drug repurposing is a real issue. Certainly in the fight against cancer, re-using existing drugs are an additional solution that should not be overlooked.
• We have published our database of repurposing candidates for cancer online at: www.redo-project.org/db. This database is constantly updated.
• We continue to publish new research in the scientific literature and work with clinicians to develop new clinical trials.