Imagine a historic building in the heart of a city. Originally constructed as a grand hotel, and it has now seen decades of use. Over the years, its purpose became less relevant, and it eventually closed its doors. However, the building’s sturdy structure, classic architecture, and prime location make it a prime candidate for renovation and repurposing. Instead of demolishing it to build something entirely new, a group of visionaries decide to repurpose the building into a modern community center.
A growing practice in the biotech industry is drug repurposing, also known as “drug repositioning” or “drug reprofiling.” Drug repurposing involves identifying new therapeutic indications for drugs already on the market. Unlike “off label” use, the goal of repurposing a drug is to seek FDA approval for an additional indication and to get medications to patient populations of critical need, such as rare diseases or during emerging threats (COVID-19). For example, only about 5% of rare diseases have an FDA-approved drug and up to 15% of rare diseases have at least one drug under current development (https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02790-7 ), which leaves many struggling families with little options for hope.
Drug repurposing offers several advantages as compared to traditional drug discovery. One key advantage of drug repurposing is leveraging the known safety profiles and pharmacokinetics of existing drugs in support of new therapeutic indications, which can result in faster and more cost-effective ways for drug approvals as compared to newly developed drugs. However, while drug repurposing can expedite the delivery of treatments to patients, it also presents unique challenges, particularly concerning toxicity. Regulatory agencies still require robust preclinical testing, which are essential to identify any novel toxicities that might arise from the drug's new use.
Drug repurposing strategies leverages known safety profiles, established manufacturing processes, and existing pharmacokinetic and pharmacodynamic data. Despite the background knowledge, drugs designed for one therapeutic indication may exhibit unexpected adverse effects when used for another. Several factors such as differences in patient population, dose variation, route of administration and drug to drug interactions contribute to this risk. To mitigate toxicity risks in drug repurposing, Attentive Science assess the toxicity profile of the drug in context of the new indication through the conduct of preclinical studies.
Recent examples of repurposed drugs include Glucagon-like peptide-1 receptor agonist (GLP-1 RA). In fact, GLP-1 RA’s are not new, they’ve been around since 2005 for the treatment of Type 2 diabetes (https://pubmed.ncbi.nlm.nih.gov/33068776/) . There has been a spotlight on repurposed GLP-1 RA’s in the media recently;
1) Ozempic (Wegovy/Semaglutide): Initially approved for the treatment of type 2 diabetes to improve blood sugar control and reduce the risk of cardiovascular events in diabetic patients, but was later approved for chronic weight management in adults.
2) Mounjaro and Zepbound (Tirzepatide): Initially approved for type 2 diabetes, with a later indication for chronic weight management.
Historical examples of repurposed drugs include the use of sildenafil (originally developed for hypertension) for erectile dysfunction and metformin (initially an anti-diabetic drug) for cancer treatment. These successes highlight the potential of drug repurposing to revolutionize treatment paradigms across various medical fields.
There are specific goals of the toxicological study, such as identifying organ-specific toxicity, determining the maximum tolerated dose (MTD), and evaluating long-term safety. Each of these safety assessments are aligned with regulatory guidelines and requirements at Attentive Science. We utilize a variety of well-characterized test systems that are relevant to human diseases and drug responses. Our expertise in selecting the appropriate models ensures that our studies yield reliable and translatable results.
Our team has extensive experience in navigating the complex regulatory landscape of drug development and repurposing. We have a proven track record of successfully supporting biotech projects through regulatory approval. An example is our current success during an unannounced FDA surveillance inspection.
Drug repurposing holds immense potential to accelerate the development of new therapies and address unmet medical needs. However, ensuring the safety of repurposed drugs is paramount. Attentive Science is well positioned to meet your preclinical testing needs with dedicated services ranging from formulation / pharmacokinetic screening, through to toxicology and safety pharmacology studies.
For more information on our preclinical research services and how we can support your drug repurposing efforts, please contact us at [https://attentivescience.com/contactus].