In the rigorous marathon of drug development, where financial investments often exceed billions of dollars and research timelines stretch over a decade, the concept of drug repurposing is quietly revolutionizing the pharmaceutical landscape. This innovative approach proves to be particularly advantageous for rare diseases, which frequently suffer from a glaring lack of treatment options. For conditions that impact fewer than 200,000 patients, the traditional drug development process can be an economically prohibitive endeavor. In contrast, repurposing stands out as a critical strategy, facilitating quicker and more affordable therapeutic solutions for ailments that have been neglected in conventional drug pipelines.
According to the National Institutes of Health (NIH), between 6,000 to 8,000 rare diseases are currently recognized, yet a mere 5 percent have received approval from the FDA for treatments. In India alone, a staggering 96 million individuals are afflicted by various rare diseases, many of which stem from genetic factors or complications resulting from viral or bacterial infections. Alarmingly, over 70 percent of these conditions lack a definitive cure and often go unnoticed within the healthcare system. This scenario presents a significant opportunity for drug repurposing in India, where the ability to expedite the introduction of effective therapies positions this strategy as a vital focus area for the pharmaceutical industry.
Streamlined regulatory pathways
Potential galore
Sanjay Vyas, President and Managing Director of Parexel India, recognizes the immense potential inherent in drug repurposing. Vyas underscores that Parexel’s research and development agenda prominently features drug repurposing across various client projects, with a particular emphasis on the realm of rare diseases. “The exorbitant cost and protracted timeline associated with developing new drugs, especially for rare conditions, pose substantial challenges. Drug repurposing offers a hopeful alternative, accelerating the pathway to develop treatments for limited patient populations,” Vyas asserts.
The most noteworthy advantage of drug repurposing lies in the ability of companies to build upon existing research data, drastically minimizing the risks and costs typically linked with conventional drug discovery. “Repurposing diminishes risks, contains costs, and shortens timelines relative to traditional drug discovery methods. Furthermore, it optimizes resource allocation while maximizing returns on investment,” Vyas elaborates. This efficiency is particularly vital in the context of rare diseases, where smaller patient populations make it increasingly difficult for pharmaceutical firms to rationalize the expenses involved in crafting new medications from scratch.
The COVID-19 pandemic illustrated the global capacity for drug repurposing on an unprecedented scale, as existing treatments such as Favipiravir, Remdesivir, and Tocilizumab were rapidly adapted to combat the virus. Vyas highlights that the repurposed drugs have already undergone comprehensive toxicity testing during their development for prior uses, giving them a reputation for safety that allows for expedited approval processes and quicker market availability. “Repurposed drugs boast robust safety profiles, enabling companies to concentrate their efforts primarily on demonstrating efficacy for these new indications,” notes Vyas.
Vyas concludes his insights by emphasizing that, “The previous one-size-fits-all methodology for treating diseases is being replaced with a more personalized approach founded on a deep understanding of individual biology, disease mechanisms, and genetic factors. By analyzing diseases at a molecular level, we can seamlessly adapt existing drugs to address various conditions, thereby maximizing their therapeutic benefits.”
The role of technology in drug repurposing
Technological advancements are significantly enhancing the efficiency of the drug repurposing landscape. For example, Parexel employs advanced modeling and simulation methodologies to support first-in-human (FIH) study designs. “By simulating a range of dosing scenarios, Parexel is adept at pinpointing the most promising candidates for repurposing, thereby significantly streamlining the transition from preclinical experiments to clinical phases,” Vyas explains. These sophisticated simulations assist pharmaceutical companies in accumulating valuable data regarding the potential performance of existing medications in treating new diseases, effectively expediting the timelines and reducing costs linked to traditional clinical trials.
Moreover, Parexel has established a partnership with Partex, a data-to-drug pharma platform that harnesses artificial intelligence (AI) and big data in the drug repurposing process. According to Vyas, this collaboration aims to bolster drug developers’ ability to ascertain the clinical success probabilities of various assets within their portfolios. “By leveraging AI and big data, we can suggest alternate therapeutic indications for which a company’s existing assets might be viable,” Vyas explains. This technology-centric approach enables pharmaceutical firms to unveil newfound opportunities for repurposing established drugs, thereby accelerating the drug development process.
AI-assisted drug repurposing utilizes advanced algorithms to uncover potential new applications for existing medications. This intricate process involves analyzing extensive chemical and biological datasets to identify novel molecular targets, predict drug binding affinities, assess possible side effects and interactions, and locate patient demographics that stand to benefit from the repurposed therapies.
GlobalData’s analysis showcases the trailblazing global organizations at the forefront of innovation in this domain, scrutinizing their patenting activities across various applications and regions. More than 470 companies, including established pharmaceutical giants, technology vendors, and emerging startups, are dedicated to the development and application of drug repurposing aided by AI technologies.
Among them, Ginkgo Bioworks emerges as a distinguished patent filer in the AIdriven drug repurposing space. The company employs AI tools and software to engineer new enzymes, proteins, and drug molecules. As a pioneer in the domain of digital health, Ginkgo integrates computational design with a synthetic biology platform and ultra-high-throughput genetic engineering within their developmental and manufacturing processes.
Selectively considering application diversity, DNAnudge takes a leading position, closely trailed by the Memorial Sloan Kettering Cancer Center and Ginkgo Bioworks. BostonGene leads geographically, with MeMed Diagnostics and Worldwide Innovative Networking also featuring prominently within the personalized cancer medicine arena.
Challenges in drug repurposing
Despite the plethora of technological and regulatory advancements, navigating the intricacies of drug repurposing is fraught with challenges. One of the most pressing hurdles involves navigating the intricate regulatory landscape governing clinical drug development.
Vyas opines that while regulatory guidelines for both new and repurposed drugs are generally well-defined, the critical distinction resides in the clinical trial stages mandated for approval. “For repurposed drugs, early-stage trials such as Phase 1 or 2 might suffice, provided that there is pre-existing safety information available on the compound,” explains Vyas.
Dr. Vikram Venkateswaran, Partner at Deloitte India, accentuates the pressing necessity for a fast-tracked pricing approval process, accompanied by an exclusive pricing framework for repurposed drugs under the National Pharmaceutical Pricing Authority (NPPA). However, he contends that India’s regulatory framework has yet to fully adapt to support drug repurposing initiatives. “While the New Drugs and Clinical Trials Rules 2019 have improved the response times, an absence of a distinct regulatory pathway specifically for repurposed drugs persists, leading to protracted approval durations and inflated costs,” states Dr. Venkateswaran.
Lack of awareness: Conversely, Prasanna Shirol, co-founder and Executive Director of the Organisation for Rare Diseases India (ORDI), underscores the urgent need for heightened awareness within the medical and scientific communities regarding the potential advantages of drug repurposing. “Investigating existing approved generic or orphan drugs to treat additional rare conditions is a more viable route than pursuing new drug development,” Shirol argues. He also advocates for the establishment of educational policies designed to facilitate swifter market authorization for repurposed drugs. “Enhanced awareness within the medical and scientific communities is vital to create a systematic listing of products and indications,” Shirol reiterates.
Unsustainable costs:While the benefits of drug repurposing are clear, pricing remains one of the most formidable challenges facing this field. Repurposed drugs, particularly those aimed at treating rare conditions, frequently carry exorbitant costs that are unmanageable for the average patient. Venkateswaran highlights that treatments such as eculizumab, utilized for rare blood disorders, are unreachably priced despite their availability on a global scale. “To address this situation, India should explore differential pricing models coupled with government-supported reimbursement initiatives,” he proposes, noting that schemes like Ayushman Bharat could be broadened to encompass therapies for rare diseases at negotiated prices. “The National Policy for Rare Diseases (2021) currently promises financial assistance of up to Rs 20 lakhs (~$24,000) for treatments, but this support should be extended to cover all repurposed drugs that demonstrate proven efficacy,” he insists.
Sagar Pawar, Partner and Lead for Life Sciences & Medical Devices at KPMG in India, elaborates on current pricing trends. “Due to orphan drug status, initial prices often skyrocket upon obtaining regulatory approval for rare disease therapies,” Pawar explains. He observes that geographical pricing disparities coupled with restricted financial returns from small patient populations limit potential funding for repurposing endeavors. He adds, “Pharmaceutical companies encounter hurdles when attempting to redirect funds toward repurposing medications for rare diseases because of the small patient demographic and insufficient financial returns. These constraints particularly impact smaller entities and nonprofit organizations that strive to bring these essential medicines to market. The absence of patent protection alongside competition in the generic drugs market further complicates recouping costs of development.”
Tapping into opportunity
To navigate these obstacles, Dr. Venkateswaran argues that expedited approval timelines and the mitigation of barriers for clinical trials involving repurposed drugs—such as allowing for more adaptive trial designs—are essential. “Advocating for a distinct category for repurposed medications under the Central Drugs Standard Control Organisation (CDSCO) could yield significant benefits. A model akin to the US FDA’s ‘505(b)(2)’ application process could permit repurposed drugs to circumvent a large segment of the conventional approval framework,” he notes.
While the impetus for drug repurposing is evident in India, the progress remains gradual. Dr. Venkateswaran points to the innovative adaptation of GLP-1 agonists, which were originally designed as anti-diabetic treatments but have since transitioned into anti-obesity interventions. These therapies have made a substantial impact globally, and he believes that India is poised to emulate this success across various therapeutic domains. “Investor enthusiasm for repurposed drugs in India is currently moderate but is steadily growing, particularly within oncology and infectious disease sectors,” Venkateswaran observes.
A pivotal element for luring further investment into drug repurposing projects in India lies in fostering collaboration between the public and private sectors. Venkateswaran advocates for India to model itself after its successful vaccine development strategies, utilizing public-private partnerships to consolidate resources efficiently. “Joint funding initiatives could significantly bolster drug repurposing endeavors in India,” he articulates, adding that incentives, including expedited approval processes and tax benefits, could also stimulate increased investment. He emphasizes the potential role of the Biotechnology Industry Research Assistance Council (BIRAC) in championing drug repurposing initiatives. “BIRAC could establish a dedicated funding mechanism for drug repurposing, especially within the domain of rare diseases,” he recommends.
Despite the existing challenges, the promise of drug repurposing represents a unique opportunity for the pharmaceutical sector, particularly in India. “Collaborative initiatives among multiple partners can pool valuable resources and expertise, facilitating the navigation through the complexities inherent to drug repurposing. For example, the CURE ID platform fosters collaboration by enabling clinicians to exchange data related to off-label uses of established drugs.” states Pawar.
“As the world’s foremost manufacturer of generic medicines, India is strategically positioned to capitalize on the advantages of drug repurposing. This pathway could accelerate the availability of treatments for future diseases, such as COVID-19, especially given that these repurposed drugs would already be globally circulated,” Venkateswaran affirms.
Dr. Venkateswaran identifies rare neurological disorders, including spinal muscular atrophy (SMA) and Duchenne muscular dystrophy, as promising avenues within the Indian context for drug repurposing efforts. “India’s vast population and genetic diversity present ample opportunities to leverage established treatments and supply chains to create a meaningful impact on the landscape of rare diseases,” he elaborates.
A path forward
Ultimately, drug repurposing presents an innovative avenue, furnishing faster and more cost-effective solutions for underserved demographic groups grappling with rare diseases. By harnessing existing research and streamlined regulatory processes, this strategy aims to enhance accessibility to efficacious treatments for millions of individuals.
In the Indian landscape, drug repurposing epitomizes a strategic approach that the pharmaceutical industry can adopt to sustain its growth trajectory while improving the reach of affordable medications. It successfully strikes a delicate balance between efficiency, affordability, and delivering effective solutions for marginalized patient populations.
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drug repurposing using real-world data
Ng healthcare professionals to share real-world evidence on the use of existing medications for new indications, thereby accelerating the exploration of repurposed therapies,” Vyas remarks.
As interest in drug repurposing grows, the call for more supportive regulatory frameworks and enhanced awareness becomes imperative. Adapting existing drugs for new uses not only addresses unmet medical needs but also holds the potential to significantly reduce development timelines and costs. The combination of advanced technological solutions and collaborative efforts between various stakeholders is likely to unlock greater efficiencies and results in the drug development landscape, ultimately benefiting patients around the world.
