'25 at 25': Extending the use of drugs - repurposing and beyond

16 Dec 2024

While much of the media coverage of advances in medicine relates to new drugs, finding new uses for existing drugs can lead to remarkable improvements for patients, often at a fraction of the cost of new drugs. As the final instalment of our 25 at 25 series, highlighting 25 achievements from 25 years of the MRC Clinical Trials Unit at UCL, we look back at some of the successes of trials we have run that have tested using drugs beyond their original licence.

Using drugs developed for treatment to prevent disease

We have conducted several trials that have found that drugs usually used to treat a disease can also be used to prevent it, when taken as prophylaxis. One notable example of this is the PROUD study, which found the antiretroviral drug Truvada, usually used as part of a combination of drugs to treat HIV, can prevent people from being infected with the virus. When taken as daily pre-exposure prophylaxis, it reduced the risk of infection for men who have sex with men in the UK by 86%.

The CHAP and ARROW trials found that children living with HIV benefit from taking the low-cost antimicrobial drug cotrimoxazole to prevent infections. The CHAP trial showed that children of all ages with symptoms of HIV should take cotrimoxazole, even in areas where there is known resistance to this drug, as it reduced the death rate by 43% compared to the placebo. ARROW showed that continuing cotrimoxazole prophylaxis reduced hospital admissions and malaria even in children who had been on ART for more than 2 years. This led to WHO recommending continued use of cotrimoxazole prophylaxis until adulthood for children living with HIV in areas with high prevalence of malaria or severe bacterial infections.

The REALITY trial showed that a bundle of drugs, usually used to treat infections, could prevent infections and reduce deaths among people starting HIV treatment with advanced disease. The bundle of drugs, which included isoniazid, fluconazole, azithromycin and albendazole, reduced the risk of death by 27%. People receiving the bundle were also less likely to have severe AIDS illnesses, abnormal test results or require admission to hospital.

Using drugs developed for different diseases in new disease areas

The drug bevacizumab was first used for treating colorectal cancer. The ICON7 trial tested adding bevacizumab to standard treatment for ovarian cancer. It found that adding bevacizumab improved overall survival by 4.8 months in women with high-risk ovarian cancer.

Another example of this comes from the PATCH trial. High risk prostate cancer is usually treated with hormone therapy Standard hormone therapy injections can cause a range of long-term side effects. A very common side effect is hot flushes, which can have an enormous impact on quality of life. Other side effects include thinning of the bones, which may lead to them becoming fragile (osteoporosis) and more likely to break. Hormone therapy injections may also increase the risk of developing diabetes or heart disease in the future.

An alternative way of giving hormone therapy is through transdermal oestradiol patches. They contain a hormone called oestradiol, which can enter the body by passing through the skin. Oestradiol also lowers the body’s testosterone levels. Researchers therefore believed that oestradiol patches may be able to treat prostate cancer in a similar way to standard hormone injections, without causing some of the side-effects. The PATCH trial tested a type of hormone patch, currently used to treat the symptoms of menopause, for controlling prostate cancer. It found the hormone patches were as good as hormone injections for people with cancer that has not yet spread elsewhere in the body. Hormone patches could increase the treatment options available for people with prostate cancer, allowing them to choose a hormone therapy approach that is best suited to them individually, in terms of the side-effects profile and how the treatment is delivered.

Another example of using a drug in a new disease area is the use of remdesivir for treating COVID-19. Remdesivir was originally developed to treat Ebola and Marburg virus infections, but during the first part of 2020 researchers in the ACTT-EU/UK trial tested it for people hospitalised with the virus. The trial found the speed of recovery with the drug was 32% faster than for those patients who had the placebo. Based on the results of this trial, the US's Food and Drug Administration authorised emergency use of the remdesivir for treating patients who are hospitalised with COVID-19 on 01 May 2020. Remdesivir was the first drug to be approved for treating COVID-19.

Using drugs for different populations

In cancer, new treatments are often tested first in people with advanced disease, but they may also offer benefits to people with earlier stage disease. Examples of the success of this approach include the STAMPEDE trial’s work testing the effectiveness of docetaxel, a chemotherapy drug, for people whose prostate cancer is still responding to hormone therapy. STAMPEDE found adding docetaxel to standard treatment helps patients with prostate cancer to live for longer without their disease coming back or getting worse. STAMPEDE also found that giving the hormone therapy drug abiraterone at an earlier stage helps men with high-risk prostate cancer to live longer.

Most drugs are tested first in adults, but children also need effective treatments. The Unit has been a pioneer in expanding treatment options for children living with HIV. This involves testing drugs that are already used in adults living with HIV, and working out what doses are safe and effective for children.

Using different doses, frequency or duration of treatment

When a drug is licenced for a condition, the licence includes details of the dose, frequency and duration of treatment. But there may be ways of refining the dose, frequency or duration of treatment. This could be reducing the dose, frequency or duration of treatment in the hope that it will improve quality of life while maintaining disease control. One example of this is the CAP-IT trial, which found that 3 days of the antibiotic amoxicillin were as good as 7 days for children being discharged from hospital with community-acquired pneumonia.

Extending the use of existing drugs poses challenges in terms of getting the results into policy and practice. But, as the examples described in this article show, it can be a fruitful approach, improving outcomes for patients and the public.

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