By Barbara A. Binzak Blumenfeld, Ph.D., M.A., Esq., Buchanan Ingersoll & Rooney PC
It is common knowledge that the process of bringing a new drug to market is time consuming and costly – an average of $1.3 billion investment1 for the research and development of a single drug product. Yet rarely is a new drug the optimal version of that product, and drug companies often search for new uses, new users, or new dosage forms of an approved product after it hits the market in what is commonly known as “drug repurposing.”
Drug repurposing is not a new concept. However, the COVID-19 pandemic prompted many companies to consider whether a drug approved for one indication had a place in doctors’ and pharmacists’ armamentarium of treatment options for this emerging disease. The antiviral medication Remdesivir, originally developed to treat hepatitis C, was one of the most high-profile repurposed drugs to emerge during the pandemic, receiving both an emergency use authorization and an approval from the FDA for the treatment of COVID-19 patients.2
Successful drug repurposing requires vision and intentionality. To receive FDA approval for a repurposed drug, companies must submit bridging studies that often include clinical trials. An application for approval of an existing drug for a new indication or in a new patient population, for example, must demonstrate that drug’s safety and efficacy under the new conditions of use. Likewise, the study of a new dosage form in the same patient population for the same indication must also demonstrate the drug’s safety and efficacy. What those studies look like — particularly in the emerging age of clinical trials focused on “patient centricity” — will vary greatly. Therefore, drug sponsors should be aware that repurposed drug development requires the same careful planning as it does for a branded new drug.
Moving Drugs To The Next Generation
Despite the time and effort spent bringing a new drug to market, these drugs are often not the ultimate version of the product that may be marketed years later. New drug sponsors proceed with development of a product for a particular condition of use, in a particular dosage form and dosing regimen, and for a specific patient population by studying the product in human clinical trials. Yet these clinical trials merely provide a snapshot of a drug’s performance under controlled and limiting circumstances. As more patients use a drug following approval, we learn more about that product because these individuals are taking other medications or have additional comorbidities that may have been carefully controlled during clinical trial enrollment. Physicians may also begin to use the brand drug off-label, therefore learning more about a drug’s potential effects on other medical conditions. Such was the case with sildenafil (Viagra). While initially developed to treat angina and hypertension, Viagra is FDA-approved for the treatment of erectile dysfunction.
Although a drug sponsor may think about repurposing its own product, that company may look to do the same thing by studying another company’s drug. A drug sponsor that repurposes another company’s product will rely on brand drug data, published literature, contemporary safety data, and appropriate bridging studies. There is no singular approach to acquiring the data required for a repurposed drug, which will vary depending upon the product and the changes introduced. The key consideration is scientifically and medically supporting the change in the repurposed drug product by relying on the original drug’s approval data and then “bridging” that data to the repurposed drug under the new conditions of use. Although bridging studies may take the form of pharmacokinetic or bioequivalence studies, in many cases FDA will require the completion of at least one clinical trial to support approval of the repurposed drug. Understanding the nature and impact of the product changes — and what supporting data FDA will need to see — is therefore critical to receiving approval for a repurposed drug.
Key Considerations In Development Of Repurposed Drugs
Pharmaceutical companies looking to repurpose approved drug products should keep several important considerations in mind.
What value am I adding if I repurpose this drug product?
This is the most critical threshold question to answer before deciding to pursue a repurposed drug development program. Repurposing drugs can be a way to speed development and reduce development costs,3 but it still requires significant time and financial investment. A repurposed product must add value for patients or physicians. For example, the change from a tablet to a capsule may not make a meaningful treatment difference, but the change from a solid to a liquid dosage form may help children or elderly patients who have difficulty swallowing a solid tablet. Determining the market for a repurposed drug requires sophisticated and honest analysis before embarking on a development program that will provide little value to patients, physicians, or the company.
What evidence of safety and efficacy will FDA require for the repurposed drug product?
The changes to an existing drug product to create a repurposed drug can be many and varied. Accordingly, there is no single way to approach the studies that will be required for FDA approval. Any repurposed drug will require bridging studies, and many repurposed drugs will require clinical trials. Drug companies should therefore engage with FDA early to address these development pathways, as it can be difficult to pivot once subjects are already enrolled.
Who do I need to engage to have a successful repurposed drug development program?
Generally speaking, all but the largest pharmaceutical companies will require outside support to accomplish their drug repurposing objectives. This support may include assistance from key opinion leaders who can assess whether it makes practical sense to repurpose a product in the first place and, if so, what changes to the brand drug make the most clinical sense. It may also include specialized advisors who can work with insurance providers to determine what evidence those providers will require to be able to cover the cost of a repurposed drug product. Finally, assistance may be needed with bridging study development as well as clinical trial protocol design and execution.
Legal advisors are also a beneficial resource throughout this process. This includes developing a drug repurposing strategy that can take advantage of FDA-provided exclusivity or expedited FDA review pathways, managing the unique contractual terms between the development partners, and working with sponsors and FDA on the regulatory requirements for approval.
When clinical trials are required, there are varying models available, from a traditional clinical trial site-focused approach to a decentralized, patient-centric approach. In the case of decentralized clinical trials, sponsors will likely need a contract research organization (CRO) that is equipped to handle unique trial features, which brings us to the next consideration.
Should I use a decentralized clinical trial design?
COVID-19 has significantly impacted the ability of drug sponsors to conduct clinical trials, whether for new or repurposed drugs. The pandemic slowed the number of new clinical trials being initiated, as well as the number of new drug applications being submitted.4 For those clinical trials that did continue, they often required a shift in how those studies were conducted to accommodate clinical trial sites temporarily closing or imposing additional safety protocols.5 As a result, the concept of decentralized clinical trials has gained momentum due to the promise of better subject enrollment and diversity as well as better convenience for the subjects.
The successful use of a decentralized clinical trial for a repurposed drug bridging study requires careful planning, as these trials raise new management concerns that can blur the lines between traditional sponsor and principal investigator roles. Drug sponsors will likely need to rely on CROs or other clinical trial management groups that can handle the required in-home subject visits, data management, and data access, and help manage the role of a principal investigator who may be increasingly relying on data received during remote subject visits. Although some COVID-era clinical trials were forced to adapt how they were managed, as a practical matter decentralized trials should be carefully planned and used from the outset of a clinical trial, and not simply be considered a “Plan B” approach if a more traditional clinical trial approach fails.
Drug repurposing should be approached with the same intentionality and focus as the development of a new branded drug product. Although the approval requirements may look different, repurposed drugs must still be safe and effective. Considering the difficult questions and planning ahead of time are therefore critical components of drug repurposing success.
- Wouters, O.J., McKee, M., and Luyten, J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA 323(9):844-853 (March 3, 2020), available at https://jamanetwork.com/journals/jama/article-abstract/2762311
- FDA News Release, “FDA Approves First Treatment for COVID-19” (Oct. 22, 2020), available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19
- Sultana, J. et al. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front. Pharmacol. 11:588654 (Nov. 6, 2020), available at https://www.frontiersin.org/articles/10.3389/fphar.2020.588654/full
- Nishiwaki, S. and Ando, Y. COVID-10 Pandemic and Trends in Clinical Trial: A Multi-Region and Global Perspective. Front. Med. 8:812370 (Dec. 24, 2021), available at https://www.frontiersin.org/articles/10.3389/fmed.2021.812370/full
- FDA, Guidance for Industry, Investigators, and Institutional Review Boards, “Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency” (updated Aug. 30, 2021), available at https://www.fda.gov/media/136238/download
About The Author:
Barbara A. Binzak Blumenfeld, Ph.D., Esq., is a shareholder in the FDA & Biotechnology practice group at Buchanan Ingersoll & Rooney PC in Washington, DC. She helps clients make and execute on strategic decisions about FDA-regulated product approvals. She integrates science and biomedical ethics into her legal practice and frequently works alongside Buchanan’s IP attorneys to create a holistic IP/FDA strategy. Binzak Blumenfeld has worked with clients on virtually all types of FDA-regulated products, including drugs (human and veterinary), biologics, regenerative medicine (cell and gene therapies), medical devices, foods (human and veterinary), and combination products.