In the recent battle against COVID-19, researchers faced a time-sensitive challenge to rapidly develop an effective antiviral drug treatment ensuring safety and efficacy. This urgency led to an increased focus on a powerful strategy: drug repurposing.
That’s when researchers investigate new indications for already approved drugs or advance previously studied but unapproved drugs for new uses.
A standout example is Pfizer's Paxlovid, a two-drug combination of Nirmatrelvir and Ritonavir. Nirmatrelvir, while specifically developed to combat COVID-19, is paired with Ritonavir, an established drug initially designed for HIV treatment. This approach underscores the value of drug repurposing in providing efficient, cost-effective solutions against evolving global health crises.
Why repurpose existing drugs?
Compared to 10% of new drug applications making it to market, some reviews found that about 30% of repurposed drugs were approved for commercial market. The World Health Organization supports repurposing, calling it “the underrated champion of sustainable innovation” in a 2021 report.
Since drug repurposing, also known as drug repositioning or reprofiling, involves identifying new therapeutic uses for drugs initially developed for different indications or diseases, it offers many advantages
- Efficiency and cost-effectiveness: Since the safety and pharmacological profiles of repurposed drugs are already established, researchers can bypass the early stages of drug development, saving significant time and resources.
- Faster time to market: By leveraging the known safety profile and previous research, drug repurposing can accelerate regulatory approval, translating to more rapid deployment of the therapy to patients in need.
- Broader treatment options: Drug repurposing can potentially provide new treatments for diseases that currently have limited treatment options.
Because of these reasons, drug repurposing is a crucial part of drug development, particularly when time is of the essence, such as during the COVID-19 pandemic.
A Case Study: Paxlovid and COVID-19
While numerous approved drugs were tested for use against COVID-19, Pfizer's antiviral Paxlovid is an example of successful drug repurposing – it showed 89% efficacy in reducing hospitalization and death.
Actually, Paxlovid is a partially repurposed drug – one of its two active ingredients, Nirmatrelvir, was developed by Pfizer specifically for the treatment of COVID-19. But it was developed using a repurposing strategy in which existing drugs were screened for activity against the main protease of the SARS-CoV-2 virus. Nirmatrelvir blocks the activity of the main protease, essentially disabling the virus’s ability to replicate.
Nirmatrelvir is delivered in combination with Ritonavir, a drug originally developed for the treatment of HIV. Ritonavir works by inhibiting certain enzymes that would otherwise break down antivirals too quickly. By including Ritonavir in the combination, it was possible to increase the concentration of Nirmatrelvir in patients' bodies, thereby improving the overall effectiveness of the treatment. During the COVID-19 pandemic, when rapid responses were of utmost importance, this innovative use of Ritonavir made a significant difference. It not only shortened the time required to develop an effective treatment but also increased the treatment's potency against the novel virus. This example showcases how drug repurposing can not only streamline the drug development process but also enhance the therapeutic potential of newly developed drugs.
The case of Paxlovid underpins the critical role that drug repurposing played in the global response to the COVID-19 pandemic and sets a powerful precedent for future responses to emerging health crises.
Spotfire™: A Powerhouse for Data Analysis in Drug Repurposing
In the complex world of drug repurposing, sorting through large datasets to identify promising candidates for repositioning can be a daunting task. Innovative data analytics tools like Spotfire, offered by Revvity Signals Software Inc., can expedite this process by simplifying complex data analysis.
Spotfire was utilized in a significant drug repurposing study aimed at identifying potential treatments for SARS-CoV-2. The solution was leveraged to calculate "Percentage of Control" (POC), a measure used to compare the level of infection in samples treated with candidate drugs versus DMSO vehicle control samples treated with a neutral agent. A compound yielding a POC below 40% demonstrates a significant reduction in infection levels compared to controls—a desirable outcome for a drug repurposing study. However, to ensure the hit compounds are not toxic to the cells, the viability of the cells must also be taken into account. Therefore, compounds with POC below 40% and viability greater than 80% were selected as the candidate hits.
The Impact of Spotfire™ in Drug Repurposing
Spotfire's capability to handle and analyze massive volumes of data, targeting very specific criteria such as the POC/viability combination mentioned above, has proven invaluable in the field of drug repurposing. An example of this can be found in a study published in Cell Reports, which aimed to identify new antiviral candidates to combat the SARS-CoV-2 virus.
The study involved screening a repurposing library of approximately 3,000 drugs (1,000 FDA-approved drugs and 2,000+ drug-like molecules), aiming to identify those that displayed antiviral properties. The utilization of Spotfire™ in this process enabled researchers to effectively sort through this vast amount of data and identify key findings. They discovered that the sensitivity to drugs and the entry pathways used by the SARS-CoV-2 virus differed significantly across cell types, with major differences observed in lung epithelial cells.
Further utilizing Spotfire's advanced analytics and visualization capabilities, the study identified nine antiviral drugs that demonstrated efficacy in respiratory cells. Among these, seven had been previously administered to humans, and three already had FDA approval. One of these, cyclosporine, was found to target Cyclophilin rather than calcineurin, revealing crucial host targets that could potentially be rapidly implemented clinically.
Such insights not only accelerate the discovery of potential antiviral drugs but also improve our understanding of SARS-CoV-2's mechanisms. These findings underline the power of drug repurposing and the critical role that Spotfire's visualization and analytics can play in such research endeavors.
Moreover, Spotfire's capabilities extend beyond drug repurposing. Revvity's Signals VitroVivo, powered by Spotfire, simplifies in vitro studies, allowing for streamlined analysis of preclinical drug development. By offering powerful tools for managing and analyzing data, Revvity Signals Software helps drive the development of new therapeutic applications for existing drugs, ultimately improving patient outcomes and potentially saving lives.
The Future of Drug Repurposing
Given the promise demonstrated by drug repurposing in combating global health crises such as COVID-19, this approach is likely to play a crucial role in future drug development strategies. The ability to harness the potential of existing drugs – and the data and studies behind them – can lead to more efficient, cost-effective therapeutic solutions. With access to high throughput screening (HTS), delivered via Spotfire™ as well as Signals VitroVivo, drug development can be expedited, providing the medical community with new tools they can use to combat emerging diseases and conditions.
Data analytics tools like Spotfire will continue to be instrumental in facilitating drug repurposing studies, providing researchers with the means to sift through vast amounts of data and identify promising drug candidates quickly and efficiently. This represents an emerging frontier of medicine, and its power must be harnessed to provide our medical professionals with the tools they need to provide patients with the care they deserve.
For those interested in discovering how Spotfire and other solutions, such as Signals VitroVivo, offered by Revvity Signals Software can aid in drug repurposing, reach out to us. Learn more here.