Drug Repurposing

Q1. How do you address the main challenges faced in the drug repurposing process?

Joab Williamson: One of the biggest hurdles in drug repurposing is convincing people—whether they’re investors, partners, or even physicians—that a drug with a previous life (and possibly a few bumps along the way) deserves a second chance. This can be tackled by passionately communicating the potential of the repurposed drug, backed by solid science, and ensuring everyone is on board from the get-go. On the legal side, the maze of patents and regulations should be followed with meticulous planning, making sure there are no unexpected roadblocks.

AI's POV: “Drug repurposing faces several challenges, including identifying new therapeutic uses for existing drugs, ensuring efficacy and safety in novel applications, and navigating regulatory hurdles. Researchers often struggle with limited data on off-label uses and must address the complexities of adapting existing treatments to new conditions. Additionally, securing funding and demonstrating commercial viability can hinder progress, despite the potential for significant benefits and cost savings in drug development.”

Q2. Can you share an example of a successful drug repurposing project and its impact?

Adekemi Taylor: Ketamine is a drug repurposing success story. The FDA approved it in 1970 as an intravenous anesthetic. Ketamine is a racemic mixture of R- and S-enantiomers. Esketamine, ketamine’s S-enantiomer, has a higher affinity than R-ketamine for the NMDA receptor, which is involved in the etiology of depression.

In 2019, the FDA approved intranasal esketamine to be used with an oral antidepressant for treatment-resistant depression. Esketamine represents a much-needed treatment option for an underserved condition. Research on esketamine’s mechanism of action is also expanding our understanding of depression.

Q3. What regulatory hurdles have you encountered in drug repurposing, and how have you navigated them?

Joab Williamson: Regulatory challenges can sometimes feel like threading a needle, especially when you’re repurposing a drug that didn’t hit the mark in its original use. It can be expected that the key to navigating this is early and open dialogue with regulators. By clearly outlining why this time is different and how the new indication stands on its own merits, potential hurdles can be turned into manageable steps. And of course, it is crucial to keep a close eye on the patent situation to ensure smooth sailing.

AI's POV: “Regulatory hurdles in drug repurposing often include proving the new use is both safe and effective, which can require additional clinical trials and data. Navigating these challenges involves rigorous research to meet regulatory standards, engaging with regulatory agencies early to understand requirements, and potentially working with specialized consultants. Clear documentation and robust clinical evidence are crucial for securing approvals and ensuring the repurposed drug meets all safety and efficacy standards.”

Q4. How do you see drug repurposing evolving in the future, and what factors will drive this evolution?

Adekemi Taylor: In the past, drug repurposing largely relied on serendipitous identification of new indications. The most famous example is sildenafil citrate (Viagra), which was originally developed for treating angina.

The availability of high throughput screening methods and increasingly powerful high-performance computing, as well as the accumulation of -omics data and knowledge about pathways and networks, will facilitate identifying more new indications for existing drugs.

Further advances in mathematical modeling of animal and clinical data will also save money by streamlining clinical development. For example, the FDA originally approved eculizumab for the rare disease paroxysmal nocturnal hemoglobinuria (PNH). Population pharmacokinetic (PK) and pharmacodynamic (PD) modeling leveraged data from patients with PNH to inform clinical study design and dose selection for a new indication with a shared disease mechanism, atypical hemolytic uremic syndrome (aHUS). Results from this model supported eculizumab’s subsequent approval for aHUS.

Q5. What role does interdisciplinary collaboration play in successful drug repurposing?

Joab Williamson: Interdisciplinary collaboration isn’t just a buzzword—it’s the lifeblood of successful drug repurposing. When you bring together minds from clinical research, regulatory, business development and legal fields, you get a 360-degree view of the challenges and opportunities. This teamwork ensures that sponsors are not only finding innovative ways to breathe new life into old drugs but are also ready to address any concerns from stakeholders before they even arise. It’s like having an all-star team where everyone plays their part to perfection.

Q6. In what ways have new technologies influenced your approach to drug repurposing?

Adekemi Taylor: Today, drug developers are using AI technology widely. For example, drug developers often spend an inordinate amount of time searching and summarizing their field’s biomedical research literature. AI algorithms can accelerate this process by curating and summarizing biomedical publications to identify new drug and disease targets.

In later drug development, mathematical/statistical modeling methods such as population PK/PD, physiologically-based pharmacokinetics (PBPK), and quantitative systems pharmacology modeling can integrate previously obtained preclinical and clinical data with data from studies for the new indication to support dose selection. This technology can even be used to replace some clinical studies.

AI's POV: “New technologies, such as advanced data analytics, AI, and high-throughput screening, have significantly influenced drug repurposing. AI helps identify potential new uses by analyzing vast datasets, while high-throughput screening accelerates the evaluation of drug candidates. Additionally, bioinformatics tools facilitate the integration of complex biological data, enhancing the precision of target identification and improving the overall efficiency of the repurposing process.”

Q7. How do you prioritize which existing drugs to repurpose, and what criteria do you use for this decision-making process?

Adekemi Taylor: Several factors determine which candidate drugs to prioritize for repurposing. These include unmet medical need, financial, and commercial viability, the pharmacokinetics of the drug, as well as safety profiles. For instance, an older drug that is vulnerable to drug-drug interactions (DDIs) could be a poor repurposing candidate as it will potentially interact with co-administered drugs.

Joab Williamson: Answering from a personal perspective, I would take a two-pronged approach. First, I would look for drugs where the science and mechanism of action (MOA) are well-understood, ideally with someone on our team—like our CMO—having hands-on experience with the drug in a previous trial. This familiarity gives us confidence in the drug’s potential. On the business side, we would assess the market landscape, patent situation, and partnering potential to ensure the project is commercially viable. It’s all about finding that balance between scientific promise and business opportunity. A drug is not feasibly without both.

Q8. Can you discuss how patient involvement or feedback influences the drug repurposing process?

Adekemi Taylor: Patient feedback is crucial for ensuring that the treatment meets their needs. Patient reports of side effects can also inform the drug repurposing process. For example, a drug that causes hypoglycemia as a side effect may be repurposed for treating diabetes. Furthermore, different drugs having similar side effect profiles can signify shared pharmacological targets which can help identify candidates for repurposing.

Joab Williamson:Patient involvement is important in many areas of drug repurposing. Their feedback helps focus on what truly matters in treatment, guiding decision-making and trial design. But it goes beyond feedback—patient participation in clinical trials is essential, as it allows the gathering of critical data, including samples that inform the repurposing process. This data helps understand how the drug behaves in the new indication, ensuring that the approach is grounded in real-world evidence. Finally, how the drug sponsor communicates externally is important, if a patient Googles the name of a medicine, headlines of previous failures may be alarming, so patient-facing communication is crucial to enabling the engagement in the drug.

Q9. How can we balance the thorough clinical testing required for new drugs with the efficiency and cost-effectiveness of repurposing existing ones?

Adekemi Taylor: Repurposing drugs, while time- and cost-effective, has its limits. For example, repurposing small molecule drugs for progressive or genetic diseases may merely treat symptoms, whereas new modalities such as gene therapy have the potential to be curative. Furthermore, other new modalities such as antibody-drug conjugates and targeted radiopharmaceuticals target cancer cells directly, minimizing damage to healthy tissues, unlike traditional chemotherapy. Of course, these emerging therapies may be candidates for repurposing in the future.

Joab Williamson: Balancing thorough testing with the efficiencies of drug repurposing is like walking a tightrope—you need precision, but also a bit of agility. Sponsors should leverage adaptive trial designs that allow real-time responses to data readouts, making the process both rigorous and flexible. By using existing data where possible, sponsors are able to cut down on time and costs, which makes the project more appealing to everyone from investors to regulators. It’s all about working smart while maintaining the highest standards.

AI's POV: “Balancing thorough clinical testing with cost-effective repurposing involves leveraging existing data to streamline trials, focusing on targeted studies that address new indications. Utilizing adaptive trial designs and leveraging real-world evidence can reduce time and costs. By building on established safety profiles and using advanced data analytics to guide trial design, researchers can efficiently bridge the gap between thorough testing and the benefits of repurposing existing drugs.”

Q10. What strategies do you employ to overcome potential intellectual property and patent issues when repurposing a drug?

Adekemi Taylor: Old drugs often have run out of patent life. Establishing a new indication with an already approved drug or drug combination can be used to acquire new intellectual property. For example, Red Hill Biopharma obtained a new patent in the US for the fixed-dose combination of the antibiotics, clarithromycin, clofazimine, and rifabutin, for treating pulmonary non-tuberculous mycobacterial infections. These antibiotics were originally approved in the 1980s and early 1990s.

Joab Williamson: Intellectual property issues can be the elephant in the room when it comes to drug repurposing. Sponsors should address this head-on with a thorough patent analysis right from the start. If conflicts are found, they can be seen as opportunities explore licensing deals or collaborations with the original patent holders to create a win-win scenario. Plus, by securing new patents for the drug’s new use, it is not only protecting the research but also to add value to the overall project, making it more attractive to investors and partners.

AI's POV: “To address intellectual property and patent challenges in drug repurposing, employ strategies such as conducting comprehensive patent landscape analyses to identify relevant patents and assess potential infringements. Engage with IP attorneys to evaluate the scope of existing patents and explore opportunities for securing patents on novel indications. Consider negotiating licensing agreements or strategic partnerships with patent holders to mitigate legal risks and facilitate access to critical IP while preserving the integrity of innovation.”

Q11. How do you assess and mitigate risks associated with repurposing drugs, especially regarding unforeseen side effects or interactions?

Adekemi Taylor: High-throughput screening and in silico methods used to identify candidates for drug repurposing can also reveal off-target activities that could lead to adverse effects. If not done at the time of initial approval, in vitro experiments can identify the risk of DDIs.

If the new indication requires higher doses than previously approved, relevant animal experiments should be performed to assess safety with the increased drug exposures, and clinical studies should be designed to assess the safety of the higher doses.

In addition, population PK and PK/PD modeling can aid in selecting the dose regimen that balances safety and efficacy. This approach is also helpful for assessing the need for dose adjustment in different patient populations. Similarly, PBPK modeling can help assess the risk of DDIs and the impact of renal/hepatic impairment on drug exposure.

Joab Williamson: In drug repurposing, mitigating risks is all about being proactive. Alongside the patent exploration, the clinical team should be deep diving into the drug’s existing safety profile and investigating how it might behave in the new context. But it’s not just about the science— it is important to stay ahead of potential regulator concerns by maintaining open lines of communication and being transparent about the existing data. By addressing issues early and being ready to adapt, you can minimize surprises and keep the project on track.

AI's POV: To effectively address risks in drug repurposing, perform in-depth preclinical and clinical studies to uncover any unexpected side effects or interactions. Utilize advanced predictive analytics and simulation techniques to forecast potential adverse reactions. Continuously refine safety measures based on the latest findings, maintaining thorough oversight throughout the repurposing process to ensure patient safety and maximize therapeutic benefits.”

Q12. In your opinion, how can industry stakeholders better support drug repurposing initiatives to maximize their success and impact?

Adekemi Taylor: Regulatory agencies can encourage drug repurposing by removing existing barriers and providing accelerated pathways. Pharma and biotech leaders can also prioritize drug repurposing as an efficient, cost-effective means for more quickly delivering medicines that fulfill unmet medical needs. For venture capital firms, drug repurposing is an attractive lower-risk prospect given the established safety profiles and drug knowledge. Industry scientists should also continue developing methods to accelerate the identification of new indications for existing drugs.

Joab Williamson: For drug repurposing to really take off, the industry needs more than just good ideas—we need a concerted effort from everyone involved. Industry stakeholders can play a huge role by fostering collaboration and regulators offering incentives that make these projects viable. Simplifying regulatory pathways and offering clearer guidelines on intellectual property issues would go a long way in encouraging innovation. Additionally, larger pharmaceutical companies which often hold left-over patent rights from failed projects, or acquisitions could be more open to partnerships with smaller companies. Ultimately, it’s about creating an ecosystem where repurposed drugs can thrive and make a real difference in patients’ lives.

Thank you for joining us for this insightful discussion on drug repurposing. We’ve explored key questions with our panelists, Adekemi Taylor and Joab Williamson. We appreciate your engagement and look forward to the continued progress in this exciting field.

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