For most people, the word recycling brings to mind plastic bottles or paper; but recycling drugs, or rather repurposing them, is as significant and far more revolutionary. As the COVID-19 pandemic has proven, finding new uses for existing drugs is faster, more cost-effective, and a potential source for future breakthroughs. With these clear advantages, a new era in drug discovery and production has begun. Using powerful algorithms and well-honed expertise, pharmaceuticals and entrepreneurs are finding the best ways to tap into the strong potential hiding right under our noses.
The What and the Why
This method of drug development goes by many names: drug repurposing, repositioning, or reprofiling. The term refers to a strategy for identifying new therapeutic uses for existing drugs that are outside the scope of their original medical application. Drug repositioning utilizes the combined efforts of experimental and computational approaches to identify or develop new uses of drug molecules.
In recent years, many pharmaceutical companies are developing new drugs with this approach. About one-third of the new drug approvals correspond to repurposed drugs, which currently generate around 25% of the annual revenue for the pharmaceutical industry. Approximately 30% of the US Food and Drug Administration (FDA) approved drugs and vaccines are repurposed. Young companies are increasingly focusing on drug repurposing, such as Singapore-based Gero and American Advaita Bioinformatics, the latter of which has received several important fundings amounting to millions of dollars for research and development of drug repurposing.
The Pros and the Scanty Cons
If there is one case that demonstrates the incentive for repurposing instead of developing new drugs from scratch, it is the coronavirus pandemic. When COVID-19 broke out, doctors and scientists considered every drug they could think of to fight the virus and its deadly symptoms. Soon, clinical trials were testing everything from Zithromax to aspirin, hoping that drugs from humanity’s vast pharmaceutical arsenal could be successfully repurposed in the fight against the virus. Any promising compounds would be taken straight into clinical trials, since companies already had enough data on their safety. One drug – Gilead’s antiviral remdesivir – was approved globally to treat COVID-19.
Even when not in a state of urgency, there are many benefits to drug repurposing. The strategy eliminates most of the risks that come from developing a new drug and drastically speeds up the time to get the medicine approved. It is highly efficient, time-saving, low-cost and with minimum risk of failure. In contrast, traditional drug discovery searches for new molecular entities – a lengthy, time consuming and expensive venture. As Arnab Chatterjee, vice president of Calibr division at Scripps Research, says, doing laboratory screens for drug repurposing is relatively inexpensive, while developing a preclinical candidate from scratch is far more costly.
However, there are also some disadvantages to take into account: the chances of finding a compound with the potential to be repurposed is relatively low. In addition, it is easy to overlook molecular compounds that have been dismissed for other indications. These neglected candidates might also have not been patented, or for whatever reason failed to reach the market. In consequence, the data scanned fails to signal them as potential treatments, even though they might be beneficial against the disease of interest.
[clinical trials are expensive; though skipping the previous steps saves time and money, these cheaper prior steps can also save money by flagging ineffective drugs. Jumping straight to clinical trials instead is a gamble of its own.]
Approaches and Techniques
Historically, and as the COVID-19 case illustrates, drug repurposing has been mostly opportunistic and serendipitous. The most successful examples of drug repurposing so far have not involved a systematic approach. Repurposing of sildenafil citrate for erectile dysfunction relied on clinical experience and insight, while repurposing thalidomide for multiple myeloma was based on serendipity. As the approach to drug development becomes more mainstream, more systematic methods are adopted.
Drug repurposing efforts can be divided into two main approaches – drug-oriented vs disease oriented. Based on the traditional approach for drug discovery, drug-oriented methodology evaluates the structural, behavioral and interactive properties of drug molecules. This strategy is meant for identifying molecules with appropriate biological effects. In contrast, disease-oriented methodology is a fresher approach; it is efficient when there is significant information on the disease model available. Companies employing this method, such as Anaxomics, are guided by the disease – its behavior, etiology, similar diseases and interacting genomics.
As drug repurposing seeks new uses for existing medicine or chemical compounds, the particularly ambitious minds set their eyes to all-rounder drugs, or drugs that work for many indications and across diverse disease areas. This “recycling” approach has been seized upon enthusiastically and effectively in oncology, where drugs originally developed to treat one form of cancer are applied to other tumor types. This is the case with Merck’s Keytruda (pembrolizumab). It was first approved for melanoma in 2014; today, this immunotherapy is used for a total of fourteen cancer types, from lung and cervical cancers to lymphoma. The pharmaceutical giant hopes to stretch even further Keytruda’s applicability, including breast cancer and other oncological conditions.
The ideal wonder-drug would expand to even more diverse pathologies, as is true of Aspirin, also called the wonder drug. This pain reliever officially named acetylsalicylic acid has clinical benefits not only in cancer, but far beyond; it has proven useful in both preventing heart attacks and in increasing survival rates during the attack itself.
To attain these goals, drug repurposing must ally with the forefront of technology. An important component is computational power. Massive stores of drug libraries must be scanned, genomes sequenced, and diseases classified and analyzed. Repurposing existing drugs is extremely dependent on big data and artificial intelligence (AI), for which new companies are beginning to specialize. AcuraStem uses AI to find applications for approved drugs or clinically validated candidates, focusing on immune-oncology, neuroscience, and rare diseases. Similarly, Austrian Delta 4 conducts in-silico screening of potential drugs, allowing researchers to test out new drugs for novel indications.
The globalization of information and significant scientific and technological advances are making drug repurposing possible; in a world where new diseases emerge at an accelerating rate and the population is only aging, drug repurposing is inevitable. This compelling approach to pharmacology is not only revolutionary, but also riddled with opportunities for ambitious scientists and entrepreneurs.