Drug Repurposing: Unlocking access to rare solutions

In the marathon of drug development, where billions of dollars and over a decade of research are the norm, drug repurposing is quietly reshaping the landscape. This approach is particularly beneficial for rare diseases, where the treatment options are woefully limited. For conditions affecting fewer than 200,000 individuals, traditional development is economically daunting and repurposing emerges as a pivotal strategy, offering faster, affordable solutions for conditions that have long been left behind in traditional drug pipelines.

According to the National Institutes of Health (NIH), of the estimated 6,000 to 8,000 known rare diseases, only about 5 per cent have FDA-approved treatments. According to a report from the Ministry of Health and Family Affairs, approximately 96 million people in India are affected by various rare diseases, many of which are genetic or acquired through viral or bacterial infections. Over 70 per cent of these conditions lack a cure and often go unnoticed, presenting a significant opportunity for drug repurposing in India. In this context, the ability to bring effective therapies to market more quickly and at lower costs, positions drug repurposing as a crucial focus for the pharmaceutical industry.

Streamlined regulatory pathways 

One of the biggest enablers of drug repurposing is the regulatory framework designed to expedite approvals for already-approved compounds. The FDA’s 505(b)(2) pathway and the European Medicines Agency’s (EMA) Hybrid Pathway offer routes for drug developers to rely on previously submitted clinical data, cutting down approval times significantly. According to research from Alacrita, a pharma and biotech consulting firm, between 2013 and 2018, nearly 50 per cent of all New Drug Applications (NDAs) approved by the FDA were based on the 505(b)(2) pathway. Dr Saadia Basharat of Alacrita in her recently published article notes that these pathways can reduce approval times for repurposed drugs down to just 3 to 12 years; much shorter than new-in-man programmes that generally take between 10 to 17 years.

Potential galore 

Sanjay Vyas, President and Managing Director of Parexel India, is among those who see significant potential in drug repurposing. He explains that Parexel’s research and development strategy includes drug repurposing for several clients, especially in the rare disease space. “The high cost and lengthy development process of new drugs, particularly for rare diseases, present significant challenges. Drug repurposing offers a promising solution, as it can expedite the development of treatments for smaller patient populations,” Vyas says.

The primary advantage of drug repurposing is that companies can leverage existing data and research, reducing the risk and cost typically associated with traditional drug discovery. Vyas elaborates, “Repurposing reduces risks, lowers costs, and shortens timelines compared to traditional drug discovery. Additionally, it optimises resource allocation and maximises returns on investment.” This is particularly important in the development of treatments for rare diseases, where patient populations are often small, making it difficult for pharma companies to justify the expense of developing new drugs from scratch. 

The COVID-19 pandemic demonstrated the potential of drug repurposing on a global scale, as treatments like Favipiravir, Remdesivir, and Tocilizumab were repurposed to treat the virus. Vyas points out that repurposed drugs have already undergone rigorous testing for toxicity during their development for other indications, meaning they are proven safe. This allows them to be fast-tracked through the approval process and brought to market more quickly. “Repurposed drugs already have a significant safety profile, which means that companies can focus their efforts on proving efficacy for new indications,” says Vyas. 

Vyas concludes, “The traditional one-size-fits-all approach to treating diseases is evolving into a more personalised strategy based on a thorough understanding of individual biology, disease mechanisms, and genetics. By understanding diseases at a molecular level, we can seamlessly repurpose drugs to treat multiple conditions, thereby maximising their benefits.”

The role of technology in drug repurposing 

Advances in technology are also playing a pivotal role in streamlining the drug repurposing process. Parexel, for instance, uses modelling and simulation techniques to support first-inhuman (FIH) study designs. Vyas explains, “By simulating various dosing scenarios, Parexel can identify the most promising candidates for repurposing and streamline the transition from preclinical to clinical phases.” These simulations allow companies to gather valuable data on how existing drugs might perform in treating new diseases, reducing the time and cost associated with traditional clinical trials. 

Additionally, Parexel has partnered with Partex, a datato-drug pharma platform that integrates artificial intelligence (AI) and big data into the drug repurposing process. The goal of this partnership, according to Vyas, is to advance the efforts of drug developers working to understand the probability of clinical success for assets in their portfolios. “By using AI and big data, we can recommend other disease indications for which a company’s assets may be clinically viable,” says Vyas. This technology-driven approach allows pharma companies to identify new opportunities for repurposing existing drugs, further accelerating the development process. 

AI-assisted drug repurposing employs sophisticated algorithms to identify potential new uses for existing drugs. This involves analysing extensive chemical and biological data to pinpoint new molecular targets, predict drug binding affinities, assess potential side effects and interactions, and identify patient populations that could benefit from repurposed therapies. 

GlobalData’s analysis highlights the global companies leading innovation in this space, evaluating the reach and impact of their patenting activities across various applications and regions. Over 470 companies, including technology vendors, established pharmaceutical firms, and emerging start-ups, are engaged in developing and applying drug repurposing AI. 

Ginkgo Bioworks stands out as a leading patent filer in AIdriven drug repurposing. The company utilises AI tools and software to engineer enzymes, proteins, and drug molecules. A pioneer in digital health, Ginkgo combines computational design with a synthetic biology platform and ultra-high-throughput genetic engineering in process development and manufacturing scale-up. 

In terms of application diversity, DNAnudge leads the field, followed closely by Memorial Sloan Kettering Cancer Center and Ginkgo Bioworks. Geographically, BostonGene takes the top spot, with MeMed Diagnostics and Worldwide Innovative Networking also prominent in the personalised cancer medicine consortium.

Challenges in drug repurposing 

Despite these technological and regulatory advancements, the journey of drug repurposing is not without its challenges. Evolving regulatory frameworks: One of the biggest hurdles is navigating the complex regulatory landscape that governs clinical drug development.

Vyas opines that while the regulatory guidelines for new and repurposed drugs are well-defined, the primary difference lies in the stage of clinical trials required. “For repurposed drugs, early-stage trials such as Phase 1 or 2 might be sufficient, provided there is existing safety data on the compound,” Vyas explains.

Dr Vikram Venkateswaran, Partner at Deloitte India, emphasises the need for a fast-track process for pricing approvals and an exclusive pricing framework for repurposed drugs under the National Pharmaceutical Pricing Authority (NPPA) to balance affordability and accessibility. However, he asserts that India’s regulatory framework is not yet fully optimised for drug repurposing. “Although the New Drugs and Clinical Trials Rules 2019 have improved timelines, there is still no distinct regulatory pathway for repurposed drugs, leading to delayed approvals and increased costs,” says Dr Venkateswaran.

Lack of awareness: On the other hand, Prasanna Shirol, co-founder and Executive Director of the Organisation for Rare Diseases India (ORDI), emphasises the need for greater awareness among the medical and scientific communities about the potential of drug repurposing. “Exploring existing approved generic or orphan drugs to treat other rare diseases is more realistic than developing new drugs,” Shirol says. He also highlights the need for India to develop policies that accommodate faster market authorisation for repurposed drugs. “There is a need for awareness among the medical and scientific community to focus on this and create a list of products and indications,” Shirol explains.

Unsustainable costs: While drug repurposing offers numerous advantages, one of the biggest challenges remains pricing. Repurposed drugs, especially those for rare diseases, often come with high costs that are unsustainable for most patients. Venkateswaran points out that treatments like eculizumab, a drug used to treat rare blood disorders, are prohibitively expensive despite their global availability. “To address this, India should consider adopting differential pricing models and government-backed reimbursement schemes,” he says, adding that programs like Ayushman Bharat could be expanded to include rare disease therapies at negotiated prices. “The National Policy for Rare Diseases (2021) currently offers financial support of up to Rs 20 lakhs (~$24,000) for treatments, but this should be expanded to include all repurposed drugs with proven efficacy,” he adds.

Sagar Pawar, Partner and Lead for Life Sciences & Medical Devices at KPMG in India, also weighs in on pricing trends. “High initial prices due to orphan drug status often lead to significant price hikes upon regulatory approval for rare disease treatments,” Pawar explains. He notes that geographical variations in pricing, coupled with limited financial returns due to small patient populations, make it challenging to fund repurposing efforts. Further he adds, “Pharma companies find it difficult to redirect funds towards repurposing drugs for rare diseases due to the small patient base and low financial returns. This limits research and development efforts, particularly affecting smaller entities and nonprofits that struggle to bring these drugs to market. The lack of patent protection and the competitive nature of generic drugs further discourage investment, as recouping costs becomes challenging.” \

Tapping into opportunity 

To overcome these challenges, Dr Venkateswaran suggests that expedited approval timelines and lowering barriers for clinical trials on repurposed drugs, such as permitting more adaptive trial designs, are crucial. “Advocating for a separate category for repurposed drugs under the Central Drugs Standard Control Organisation (CDSCO) could also be beneficial. This could be similar to the US FDA’s “505(b)(2)” application process, which allows repurposed drugs to bypass much of the traditional approval process,” he adds. 

In India, the momentum for drug repurposing is growing, but the progress has been slow. Dr Venkateswaran points to the innovative use of GLP-1 agonists, initially anti-diabetic drugs, now repurposed as anti-obesity treatments. These treatments have had a significant global impact, and Venkateswaran believes that India has the potential to replicate this success in other therapeutic areas. “In India, investor enthusiasm for repurposed drugs is moderate but gradually increasing, particularly in fields like oncology and infectious diseases,” says Venkateswaran. 

One of the key factors in attracting more investment to drug repurposing in India is collaboration between the government and the private sector. Venkateswaran suggests that India adopt a model similar to its successful vaccine development strategy, relying on public-private partnerships to pool resources. “Joint funding initiatives could significantly boost drug repurposing efforts in India,” he says, adding that incentives like streamlined approval processes and tax breaks could further encourage investment. Venkateswaran also highlights the role that Biotechnology Industry Research Assistance Council (BIRAC) could play in supporting drug repurposing efforts. “BIRAC could establish a dedicated fund for drug repurposing, particularly for rare diseases,” he suggests. 

Despite the challenges, drug repurposing presents a unique opportunity for the pharma sector, particularly in India. “Multipartner collaborations can pool resources and expertise, making it easier to navigate the complexities of drug repurposing. For instance, the CURE ID platform facilitates collaboration by allowing clinicians to share data on off-label uses of existing drugs,” states Pawar. 

“As the world’s largest manufacturer of generic medicines, India has vast potential to utilise repurposed drugs. This approach could accelerate the accessibility of treatments for diseases like COVID-19, which may emerge in the future without existing vaccines, as these drugs would already be in circulation globally,” states Venkateswaran. 

Dr Venkateswaran suggests that rare neurological disorders like spinal muscular atrophy (SMA) and Duchenne muscular dystrophy offer promising avenues for repurposing efforts in India. “India, with its vast population and genetic diversity, has the opportunity to leverage existing treatments and supply chains to make a lasting impact on the rare disease landscape,” he explains.

A path forward 

Thus, drug repurposing is an innovative approach that provides faster, affordable solutions for underserved patient groups affected by rare diseases. By leveraging existing research and streamlined regulations, this strategy aims to improve access to effective treatments for millions.

In the Indian context, drug repurposing exemplifies a strategic approach that the pharma industry can embrace to continue its growth momentum and improve access to affordable medication. It strikes a delicate balance between efficiency, affordability, and effective solutions for underserved patient populations.

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