Abstract
Background
Drug repurposing describes the approval of an already authorized medicine for a new therapeutic indication. Rising development costs, long clinical timelines and attrition in first-in-class discovery have renewed interest in this strategy as a way to extend pharmacological value using pre-validated mechanisms. This study evaluates how repurposing has contributed to pharmaceutical innovation over four decades, examining approval patterns, therapeutic redirection and industry behavior.
Methods
A longitudinal dataset of all new molecular entities and biologic products approved by the United States regulator between 1985 and 2024 was constructed. Repurposing was defined strictly as a new therapeutic indication distinct from the original approval. All cases were verified using regulatory documentation. Descriptive analyses quantified approval volumes, therapeutic transitions, applicant trajectories and development intervals. We compared the time to repurposing when development remained within the original company versus when rights transferred externally.
Results
Here we show that 451 drugs received subsequent approval for a new therapeutic use, representing a substantial fraction of authorized medicines. Oncology and neurological disorders act as major nodes of redirection, serving both as frequent endpoints and as mechanistic sources for cross-domain translation. The mean interval between first approval and repurposing is 7.2 years, shorter than typical development timelines for newly originated drugs. Repurposing occurs more rapidly when development rights remain with the original owner, and large firms account for most approvals.
Conclusions
Repurposing has become a durable component of pharmaceutical innovation, enabling faster clinical deployment of validated mechanisms across disease domains. These findings highlight its potential to expand treatment options while reducing R&D uncertainty.
Subject terms: Business strategy in drug development, Drug screening, Drug development
Akodad et al. map nearly four decades of FDA approvals to identify how authorised medicines acquire new therapeutic uses. The study shows that repurposing follows consistent regulatory and industrial patterns, highlighting its growing role in pharmaceutical innovation.
Plain language summary
Drug repurposing occurs when a medicine already approved for one disease later gains approval for a different therapeutic use. Because developing entirely new treatments is lengthy and complex, repurposing can offer a faster and more reliable route to bring effective therapies to patients. In this study, we analyzed all FDA drug approvals over the past forty years to understand how repurposing actually unfolds. We traced how medicines move across disease areas, how long these transitions take, and how often companies redirect their own products compared with external developers.
Our findings show that repurposing is a stable and meaningful part of pharmaceutical innovation, enabling established scientific knowledge to be reapplied in new ways and accelerating the arrival of new treatment options.
Introduction
Drug repurposing, defined as the strategy of identifying novel therapeutic indications for approved drugs beyond their original medical scope, has emerged as a key innovation strategy in pharmaceutical development. With the cost of bringing a new drug to market escalating to estimates between $314 million and as high as $2.8 billion and development times extending over a decade, the pharmaceutical industry faces significant challenges in its traditional development paradigms1. In this context, drug repurposing offers a promising alternative by utilizing existing compounds with established safety profiles. This approach not only reduces the risk of failure but also significantly lowers the cost and time associated with drug development.
Several reviews indicate that approximately 30% of drug repurposing efforts successfully lead to regulatory approval, a notable contrast to the roughly 10% success rate observed for new drug applications2–5. Moreover, reports suggest that de novo drug discovery and development typically spans 10–17 years, whereas repurposed drugs can achieve approval within a significantly shorter timeframe (3 to 12 years) at nearly half the cost 6,7.
The significance of drug repurposing extends beyond economic benefits; it also enhances the efficiency of pharmaceutical research and development (R&D) by leveraging the known properties of drugs, such as pharmacokinetics and pharmacodynamics (the so-called PK/PD profile), and established safety profiles. This approach not only accelerates the availability of new treatments but also maximizes the therapeutic potential of approved molecules 2.
Additionally, drug repurposing addresses the urgent need for treatment options in areas where patient populations are too small to commercially justify the expense of traditional drug development routes, such as rare diseases and orphan indications8. The COVID-19 pandemic further exemplified the utility of drug repurposing in addressing urgent therapeutic needs. Public-private collaborations play a pivotal role in driving successful repurposing initiatives. For instance, the development of remdesivir in the fight against COVID-19, initially funded for Ebola research, demonstrates how partnerships between academic institutions, government agencies, and pharmaceutical companies can accelerate the identification and approval of repurposed drugs 9.
This collaborative model not only facilitates swift responses during crises but also highlights the broader potential for aligning public health priorities with commercial drug development strategies10. By expediting the evaluation of existing drugs for new indications, researchers were able to provide timely treatment options. This underscores the broader potential of repurposing to respond rapidly in crisis situations, reinforcing its importance not only in rare diseases but also in global health emergencies.
Despite its advantages, drug repurposing faces several challenges, including intellectual property (IP) issues, regulatory hurdles, and the need for strategic market positioning. The current IP framework often fails to adequately incentivize drug repurposing, as method-of-use patents and regulatory exclusivity periods may not provide sufficient protection for new indications, discouraging investment in such efforts. Additionally, the reliance on public funding and academic research to initiate repurposing projects highlights a structural imbalance in the ecosystem, where private stakeholders are less motivated to explore off-patent or non-commercially viable compounds.
The lack of availability of active compounds, protected by patents and data exclusivities, further complicates the exploration of new therapeutic uses for these drugs, creating barriers to addressing patient needs. While these regulatory protections are essential for fostering innovation, they can inadvertently limit the repurposing potential of existing drugs by restricting access to promising compounds for third parties.
However, advancements in computational methods and extensive databases have increasingly enabled the systematic identification and validation of new therapeutic uses for existing drugs11. These technological innovations have broadened the scope of repurposing efforts and introduced a more structured approach to uncovering and developing opportunities for repurposing.
Given the increasing focus on drug repurposing as a pivotal innovation strategy, a comprehensive review of the progress achieved and the industrial organization of this field is both timely and necessary. The industrial organization of drug repurposing remains fragmented, with public and private stakeholders often operating in isolation. This fragmentation limits the systematic exploration of repurposing opportunities and underscores the need for policy reforms to incentivize collaboration 10.
This study analyzes the interplay between regulatory frameworks, market exclusivities, and innovation incentives to address these gaps and propose actionable pathways for optimizing the drug repurposing ecosystem. Specifically, it undertakes an in-depth examination of FDA-approved New Molecular Entities (NMEs) and Biologics, regulated by the Center for Drug Evaluation and Research (CDER), from 1985 to 2024. The objective is to elucidate key trends and patterns in drug repurposing by exploring the roles of public and private organizations, the prevalence of repurposing across therapeutic areas, and the shifting landscape of pharmaceutical research.
By providing evidence-based strategic insights, this study aims to identify opportunities that can inform and guide future pharmaceutical initiatives. Ultimately, it underscores the transformative potential of drug repurposing to optimize drug development processes, enhance R&D efficiency, and deliver more timely and accessible therapeutic options for patients in need.
Building on this foundation, the study develops, to the best of our knowledge, the first comprehensive dataset linking all FDA-approved CDER repurposed drugs to their originator products, allowing a detailed characterization of their therapeutic, organizational and mechanistic trajectories. This integrated view clarifies how repurposing unfolds across disease areas and industry actors, and it provides an evidence-based perspective on the strategic pathways through which existing medicines acquire new therapeutic roles. Taken together, the findings show that repurposing constitutes a consistent and meaningful component of pharmaceutical innovation, identifying opportunities to improve R&D efficiency and to expand timely access to effective treatments.
Methods
This Methods section outlines the conceptual criteria used to distinguish genuine therapeutic repurposing from incremental indication extensions, and describes how these criteria were applied to a systematically constructed FDA-based dataset.
To further illustrate how these criteria were operationalized, Box 2 provides a detailed case analysis of semaglutide (Ozempic/Wegovy), highlighting how distinct regulatory pathways can result in both incremental extensions and genuine therapeutic repurposing.
Box 1 Definition of drug repurposing.
In this study, drug repurposing is defined as the regulatory approval of an existing drug for a new, distinct therapeutic indication beyond its originally approved medical use. This definition builds on authoritative frameworks from the literature1–3 and adapts them to the FDA approval context.
To ensure methodological consistency, a case was classified as repurposing only when the following criteria were simultaneously met:
Regulatory distinction—The drug received a new FDA approval under a different indication code or therapeutic area, as documented in Drugs@FDA and FDA labeling archives.
Therapeutic shift—The newly approved indication addressed a distinct disease entity (e.g., asthma → rheumatoid arthritis; diabetes → obesity). Incremental extensions within the same physiological domain (e.g., allergic rhinitis → allergic conjunctivitis) were excluded.
Population extensions excluded—Label expansions limited to new populations (e.g., pediatric or gender-specific indications) without a change in the underlying disease were not considered repurposing.
Mechanistic continuity allowed—In oncology and other mechanism-driven fields, drugs approved for topologically distinct cancers (e.g., breast cancer → prostate cancer) were classified as repurposing if the indication targeted a different organ or tissue, even when the underlying molecular pathway (e.g., EGFR, VEGF) overlapped.
Formulation or route modifications excluded—Reformulations (e.g., oral to IV), dosage changes, or combinations without a distinct therapeutic indication were excluded.
This operational definition was systematically applied to all FDA CDER-approved NMEs and BLAs between 1985 and 2024. Each case was independently verified through Drugs@FDA and FDA Orange Book records to ensure that only FDA-approved repurposing events were retained.
Box 2 Semaglutide (Ozempic/Wegovy): an illustrative example of multi-level repurposing.
Semaglutide exemplifies how a single active ingredient can follow distinct regulatory and therapeutic trajectories, illustrating the nuanced continuum between line extension, therapeutic repurposing, and brand-level repositioning. All approvals derive from the same active compound (semaglutide), yet they differ in clinical scope, target disease, and regulatory pathway.
Incremental extension (non-repurposing). In 2020, Ozempic® received an additional FDA indication to reduce major adverse cardiovascular events (MACE) in adults with type 2 diabetes and established cardiovascular disease. This represents a population-specific label expansion within the same disease category and was therefore excluded from our dataset.
Therapeutic repurposing. In 2025, Ozempic® obtained FDA approval to reduce the risk of kidney disease progression, kidney failure, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease (CKD). This constitutes a therapeutic shift from endocrinology to nephrology, fulfilling our criteria for repurposing as it targets a distinct pathological mechanism and clinical specialty.
Brand-level repositioning. The same molecule was later marketed as Wegovy® (2021) for chronic weight management in adults with obesity or overweight and at least one comorbidity. Despite sharing the same mechanism of action (GLP-1 receptor agonism), this indication represents a new disease entity, a distinct patient population, and a new regulatory dossier. It therefore qualifies as a repurposing event under a new brand identity.
This example underscores the methodological distinction between incremental label extensions and genuine therapeutic or market repurposing. In this study, only indications that crossed disease boundaries or therapeutic domains were classified as repurposing.
Sample selection
To examine drug repurposing trends, the selected sample includes FDA-approved CDER New Drug Applications (NDAs) for NMEs and Biologic License Applications (BLAs) for biologics spanning the period from 1985 to 2024. These categories were deliberately chosen because they represent significant therapeutic innovations with the highest potential for drug repurposing. NDAs and BLAs account for submissions introducing novel mechanisms or unique biological targets, distinguishing them from other submission types such as Abbreviated New Drug Applications (ANDAs) for generics, and 505(b)(2) NDAs for modified drugs. These other submission types, which primarily address reformulations or regulatory updates, were excluded to focus solely on new therapeutic options.
Additionally, products regulated by the Center for Biologics Evaluation and Research (CBER) (including vaccines, gene therapies, and blood products tailored to highly specialized or personalized medical needs) were excluded from this analysis. Unlike CBER products, CDER NDAs and BLAs generally offer broader therapeutic potential and are thus more likely to be repurposed for additional indications.
The decision to focus on FDA-approved drugs reflects an editorial choice, as the FDA is widely recognized as the first regulatory agency to approve de novo drugs. This precedence ensures that the dataset captures the earliest and most comprehensive insights into drug repurposing opportunities. By narrowing our scope to NDAs and BLAs, the study provides a precise and relevant examination of drug repurposing trends in categories most reflective of classical pharmaceutical innovation. This exclusion of minor reformulations and non-CDER products ensures that our analysis captures meaningful shifts in therapeutic strategy and innovation over time.
Data collection and verification
The primary data source to construct the database was the FDA’s publicly available Drugs@FDA database. Each NME and Biologic was researched to determine if it had been repurposed for additional therapeutic uses. Verification was conducted through consulting literature reviews, pharmaceutical registries, and FDA records. A detailed description of data management procedures, verification steps, and the full field dictionary is provided in Supplementary Methods and Supplementary Note 2.
Verification was conducted through consulting literature reviews, pharmaceutical registries, and FDA records.
In line with the operational definition presented in Box 1, approvals representing within-class or within-site extensions (such as new treatment lines, formulations, or tumor subtypes sharing the same molecular pathway) were not classified as repurposing. Only FDA-approved indication shifts spanning distinct therapeutic or mechanistic domains were retained in the final dataset.
Analytical approach
The main trends of the data were identified based on descriptive statistics and graphs using Python. Additional Sankey diagrams were also constructed with Python to provide more detailed trends across stakeholders and therapeutic target areas. The full numerical source data used to generate these figures are provided in Supplementary Note 1.
Ethical considerations
The study adhered to ethical standards, using only publicly available data. While every effort was made to ensure accuracy, exhaustive citation of all sources was beyond the project’s scope.
Limitations
As a consequence of selecting the FDA-approved CDER NDAs and BLAs from 1985 to 2024, the number of approvals captured in this study may be lower than the total number of FDA-approved drugs (which includes CBER-regulated products). Although this intentional exclusion creates a selection bias, it highlights the targeted nature of our analysis as CDER NDAs and BLAs generally offer broader therapeutic potential and are thus more likely to be repurposed for additional indications. By concentrating on CDER-regulated products, we aim to provide a precise and relevant examination of repurposing trends where they are most likely to occur. Definitions of all dataset variables are provided in Supplementary Note 2.
Additionally, readers should note that the dataset begins in 1985, corresponding to the earliest year for which complete FDA CDER records are systematically available through Drugs@FDA. This introduces a potential left-truncation bias affecting early-decade trends. Repurposing efforts or exploratory research that began before 1985 but led to approvals soon after may thus appear with artificially short intervals or lower event counts. Consequently, time-based comparisons across decades should be interpreted as relative within the observed period, rather than as absolute representations of all historical repurposing activity.
Furthermore, by excluding drugs originally approved before 1985, our analysis overlooks older compounds that hold significant potential for genuine therapeutic repurposing. For instance, thalidomide, originally approved in 1950 as a sedative, has been successfully repurposed for leprosy and multiple myeloma, while clemastine, originally approved in 1977, is currently being investigated for promoting brain cell myelination, showing promise for neurodegenerative diseases. These older compounds, with well-documented safety and usage histories, exemplify authentic repurposing efforts, in stark contrast to certain industry practices aimed at artificially extending a molecule’s commercial lifespan. Their emerging applications highlight the critical need to recognize their value in shaping future therapeutic landscapes and suggest they should be the focus of dedicated, complementary studies.
Moreover, this focus on FDA-approved repurposed products underestimates repurposing efforts, as failed and ongoing clinical trials’ results are not included. Future studies could expand this scope to include CBER-regulated products and other therapeutic categories. Also, studying the failed or halted clinical trials focusing on drug repurposing might reveal important insights and avoid duplication of efforts. Additionally, studying the ongoing clinical trials aiming to bring repurposed products to the patient could confirm our analysis or show further evidence of the increasing impact of drug repurposing. Even more, focusing on approved therapies forgoes the existence of the off-label use market, which further increases the impact of drug repurposing on the lives of patients. However, for the purposes of this analysis, our approach offers the most pertinent insights into the current repurposing landscape.
Results
We first analyze the main trends in drug repurposing over time and link them to what the literature has shown in the last four decades. Then, we study key therapeutic areas separately to identify more specific trends. Finally, we analyze industry specificities to link the therapeutic area-activities to the market dynamics by looking into the type of organizations identified in repurposed drug approvals.
Trends in drug repurposing over time
The analysis of FDA CDER drug approval rates from 1985 to 2024 offers a comprehensive view of the regulatory landscape and the evolution of pharmaceutical innovation over the past decades. In this context, two primary submission types dominate: NDAs for NMEs and BLAs for biologics (Figs. 1–3). Both pathways are essential for understanding the dynamics of market introduction and innovation in the pharmaceutical industry. By focusing on these submission types, we can discern the underlying trends in repurposing activity, as they reflect the introduction of genuine new therapeutic options, distinct from modifications or extensions of existing compounds known as line extensions or from repurposing attempts identified during clinical trials as drugs are redirected toward alternative therapeutic targets. Such redirections can occur when a drug’s effects suggest potential benefits beyond the initially intended use, leading researchers to explore new therapeutic indications during the clinical trial phase.
Fig. 1. FDA approvals of de novo drugs via NDA and BLA pathways (1985–2024).
This figure shows the annual number of FDA-approved new molecular entities (NMEs) and Biologics between 1985 and 2024. Blue bars represent drugs approved via new drug applications (NDAs), while orange bars correspond to approvals obtained through biologics license applications (BLAs). The figure illustrates long-term trends in the introduction of de novo therapies across both regulatory pathways.
Fig. 3. Annual FDA approvals of de novo and repurposed drugs (1985–2024).
This figure compares the annual number of FDA-approved de novo drugs and repurposed drugs from 1985 to 2024. Blue bars represent de novo approvals, while orange bars indicate approved repurposed drugs. The figure highlights long-term trends in the balance between new drug introductions and repurposing activities over four decades.
However, it’s important to note that many line extensions, often used to include pediatric formulations or indications, reflect an industry trend where pediatric needs are addressed through minimal adaptations rather than genuine innovation.
Initial trends in drug development and repurposing (1985–1990)
In the late 1980s, the pharmaceutical industry was primarily driven by “the blockbuster model”. This model was focused on the development of de novo therapeutic molecules, with 20–40 drugs approved annually by the FDA, including NDAs and BLAs (Fig. 1). These drugs, primarily designed for large patient populations suffering from common non-communicable conditions like hypertension, diabetes, and cardiovascular diseases (CVD), represented high-revenue opportunities for pharmaceutical companies12. The market was heavily incentivized to prioritize such first-in-class therapies due to the extensive patent and clinical data protection granted to NDAs and BLAs, offering long-term market exclusivity and high profitability.
During this period, repurposing efforts were generally limited (Fig. 2). Pharmaceutical companies viewed novel drug development as more lucrative and strategically essential, given that the regulatory and market frameworks were more favorable toward de novo NDAs and BLAs. Regulatory protection, such as through the 20-year patent exclusivity, and the lack of computational tools for systematic drug repurposing (such as bioinformatics and genomics), further solidified the industry’s focus on de novo drugs13.
Fig. 2. FDA approvals of repurposed drugs via NDA and BLA pathways (1985–2024).
This figure shows the annual number of FDA-approved repurposed indications between 1985 and 2024, distinguished by regulatory pathway. New drug applications (NDAs) are represented in blue and biologics license applications (BLAs) in orange. Bars indicate the volume of repurposing events per year, illustrating the rise in both small-molecule and biologic repurposing over the study period.
However, despite the industry’s clear preference for new molecular discoveries, serendipity played a role in some of the earliest repurposing cases. These repurposing successes were not the result of systematic exploration, but rather the outcome of clinical observation and off-target effects, underscoring how repurposing in this era remained largely opportunistic.
Regulatory shifts and the spike in approvals (1990–2000)
The 1990s were transformative for the pharmaceutical landscape, not only because of advances in drug R&D but also due to significant regulatory shifts that profoundly impacted approval rates. The introduction of the Prescription Drug User Fee Act (PDUFA) in 1992 marked a turning point. PDUFA allowed the FDA to collect fees from pharmaceutical companies, accelerating the review process for drug applications. This expedited regulatory review resulted in a notable spike in drug approvals in 1996, driven by the clearing of a significant backlog of applications and the increased pace of pharmaceutical R&D13 (Fig. 1).
Despite the immediate surge in approvals, the late 1990s saw a decrease. This dip reflected underlying issues within the industry, despite faster approval times. The decrease in novel drug approvals can be attributed to multiple factors: the inherent complexities in developing first-in-class drugs, rising R&D costs, and the increasing difficulty in achieving breakthrough innovations12. Additionally, companies began to encounter the limits of traditional NME-focused strategies, particularly as many of their high-revenue blockbuster drugs from the 1980s were nearing the end of their patent protection: a phenomenon referred to as the “patent cliff”.
This period also coincided with growing regulatory complexity, as the FDA increased its focus on ensuring drug safety and efficacy, which lengthened the clinical trial process and raised the bar for new drug approvals. As a result, pharmaceutical companies began to explore alternative strategies to sustain revenues and extend the life cycle of their products, including line extensions and repurposing efforts. However, repurposing remained an underutilized approach at this stage, often hindered by IP concerns and the lack of systematic approaches to identify new therapeutic uses (Fig. 2).
The patent cliff and the strategic shift to biologics (2000–2010)
The early 2000s marked a critical juncture for the pharmaceutical industry as the “patent cliff” began to take effect. This term describes the period during which patents for many blockbuster drugs, such as those for cholesterol and blood pressure management, expired, leading to a sharp increase in generic competition. The resulting revenue losses prompted companies to diversify their R&D strategies, looking for ways to replenish their product pipelines with projects that reduce the high risks associated with NMEs.
Biologics emerged as a key strategic focus during this period (Fig. 1). Unlike chemically designed small-molecule drugs, biologics (therapies derived from living organisms) offered longer market exclusivity under US law (12 years compared to 5 years for small molecules), making them an attractive alternative to NMEs14. The development of biologics also aligned with the increasing biotechnological insight (e.g., due to the Human Genome Project) and the accompanying growing interest in personalized medicine. Biologics, which are often tailored to target specific molecular pathways, became particularly prominent in treating complex diseases such as cancer and autoimmune disorders. Examples include monoclonal antibodies (mABs) targeting tumor markers revolutionized cancer therapy, and TNF-inhibitors that transformed treatment approaches in autoimmune diseases like rheumatoid arthritis and Crohn’s disease.
At the same time, repurposing strategies began to gain traction, particularly in response to the rising costs and high failure rates of novel drug development (Fig. 2). During this period, the repurposing of older drugs with established safety profiles became an attractive alternative to targeting new indications, rather than developing entirely new molecules. Additionally, from 2000 onward, our analysis reveals that nearly half of newly approved FDA drugs target new indications for known products (Fig. 3), confirming the increasing interest in repurposing as a strategic R&D approach. Indeed, regulatory incentives, such as the Orphan Drug Act (ODA, 1983), Priority Review and Accelerated Approval (both introduced in 1992), encouraged companies to revisit older compounds, including for rare diseases, where traditional drug development pathways were often cost-prohibitive8. Our data shows that approximately 15% (60 out of 403) of original drugs with orphan drug designation (ODD) have undergone repurposing, reflecting a measurable—though proportionally limited—trend toward pathway-driven translation in rare diseases. Unlike NMEs, which predominantly target broader commercial markets, orphan drug repurposing develops through niche, mechanism-specific repositioning grounded in deeper biomolecular insight. This distinction suggests a shift in R&D priorities, where repurposing is increasingly leveraged when mechanistic understanding enables therapeutic extension across closely related rare disease pathways.
Biologics and the rise of personalized medicine (2010–2024)
The 2010s saw the pharmaceutical industry’s most pronounced shift towards biologics and personalized medicine. Advances in biotechnology, the development of the “omics” (genomics, transcriptomics, proteomics and metabolomics), and the shift toward precision medicine have transformed drug development, allowing for more targeted therapies that could address specific molecular mechanisms of disease. This period witnessed a marked rise in BLA approvals (Figs. 1 and 2), reflecting the industry’s growing commitment to biologics as a core component of its therapeutic arsenal 15.
Precision medicine, particularly in oncology and (rare or single-nucleotide) genetic disorders, was increasingly underpinned by genomic advancements. For example, companion diagnostics that identified specific genetic mutations, such as EGFR mutations in non-small cell lung cancer (NSCLC), enabled the development of targeted therapies with significantly improved efficacy and safety profiles16. By focusing on molecular markers rather than broad disease categories, pharmaceutical companies could streamline clinical trials by stratifying patient populations, improve success rates, and bring therapies to market more quickly.
At the same time, repurposing efforts continued to gain momentum, particularly in therapeutic areas with high unmet need (Figs. 2 and 3). For example, drugs originally approved for unrelated conditions were increasingly evaluated for new uses in oncology, rare diseases, and neurological disorders (Fig. 4), where drug development has historically faced high failure rates. Advances in bioinformatics, high-throughput screening (HTS), the maturation of big data, and its boost to artificial intelligence (AI), facilitated more systematic approaches to drug repurposing, moving away from the opportunistic discoveries of earlier decades toward a more calculated and data-driven process 2.
Fig. 4. Distribution of FDA-approved de novo drugs by therapeutic area (1985–2024).
This figure presents the number of de novo FDA-approved drugs categorized by therapeutic area between 1985 and 2024. Each bar represents a distinct therapeutic field, illustrating areas where first-in-class approvals have been most concentrated over the study period. Therapeutic areas with a single drug approval were excluded to reduce visual noise and improve the interpretability of broader trends.
COVID-19 and the acceleration of drug repurposing
The COVID-19 pandemic accelerated the industry’s reliance on drug repurposing, as the global health crisis demanded urgent therapeutic solutions. Regulatory bodies, including the FDA, adapted by providing Emergency Use Authorizations (EUAs), allowing drugs originally developed for other conditions to be rapidly repurposed for COVID-19. Remdesivir, for instance, was repurposed from its original use as an antiviral drug for Ebola to treat COVID-19 patients, providing a critical therapeutic option during the pandemic. The drug is still routinely used when an immunocompromised patient is diagnosed with COVID-19 17.
This era underscored the value of drug repurposing as a rapid response tool in public health emergencies. It also highlighted how regulatory frameworks could be adapted to fast-track approvals while maintaining rigorous safety and efficacy standards. The pandemic demonstrated the pharmaceutical industry’s capacity to innovate under pressure, blending repurposing strategies with cutting-edge biotechnology to deliver solutions at an unprecedented pace.
FDA approval trends in de novo and repurposed drugs by therapeutic area
The analysis of FDA CDER approvals from 1985 to 2024, encompassing both de novo and repurposed drugs, provides critical insight into the evolution of therapeutic priorities and the industry’s adaptive strategies to unmet medical needs. As shown in Figs. 4 and 5, the hierarchy is strikingly similar across both pathways: Oncology ranks first, and Psychiatry/Neurology consistently occupies second place. The third position diverges, with Infectious Disease more prominent in de novo discovery, while Cardiology rises in repurposing. This pattern suggests that repurposing amplifies domains with mature mechanistic understanding and well-defined endpoints (oncology; neurology), while the swap at rank three reflects pathway-specific dynamics—de novo innovation addressing pathogen-driven novelty, and repurposing leveraging class effects and pleiotropic mechanisms in cardiometabolic disease. Below the top tiers, repurposing shows relatively greater visibility in inflammation/immunity-adjacent fields (gastroenterology, rheumatology, immunology, pulmonology), consistent with cross-disease translation of immunomodulatory agents.
Fig. 5. Distribution of FDA-approved repurposed drugs by therapeutic area (1985–2024).
This figure displays the number of FDA-approved repurposed drugs across major therapeutic areas from 1985 to 2024. The chart highlights domains where repurposing activities have been most prevalent, reflecting patterns of cross-indication translation. Therapeutic areas with a single drug approval were excluded to reduce visual noise and improve the interpretability of broader trends.
To ensure consistency across the analysis, therapeutic areas were categorized uniformly for both de novo and repurposed drugs. Conditions with a genetic basis are grouped under the “genetic disorders” category, irrespective of the organ systems or clinical manifestations they affect. For example, a genetic disorder impacting the nervous system is classified as a “genetic disorder” rather than under “neurology”. This categorization reflects the study’s emphasis on the genetic basis of these conditions while recognizing that overlaps between therapeutic areas (such as between genetic and neurological disorders) are inherent to the complexity of drug development. This approach provides a unified framework for interpreting trends across all therapeutic areas, ensuring that both de novo and repurposed drug approvals are analyzed under a consistent methodology.
Oncology
Oncology stands as the leading area for de novo drug approvals, accounting for approximately 20.8% (279 out of 1336 total approvals). This strong representation underscores the pharmaceutical industry’s intense focus on cancer treatment innovation, largely driven by the high global burden of cancer, the persistent demand for novel therapeutic approaches, and a wide array of policy incentives such as grant funding, orphan designation, and expedited review pathways. According to our data, nearly half of oncology drugs approved between 2008 and 2021 leveraged the FDA’s Accelerated Approval pathway (112 out of 278), reflecting the urgency for rapid access to innovative therapies in this domain. The sustained growth in oncology drug development also reflects the increasing role of genomic profiling, immunotherapy, and targeted mechanisms, which have transformed oncology into the most dynamic and scientifically mature therapeutic field within the FDA’s regulatory landscape.
Repurposing in oncology is equally impactful and even more dominant in relative terms. With 160 repurposed drugs, oncology accounts for over 35.5% of all repurposed approvals (n = 451), underscoring the field’s capacity to redeploy pharmacological agents across related molecular mechanisms. This trend aligns with the multifactorial nature of cancer biology, where drugs initially developed for other conditions can modulate key processes such as angiogenesis, apoptosis, and immune signaling, which also drive tumor progression. Many oncology repurposings remain intra-therapeutic, extending approved agents to new tumor subtypes that share the same molecular targets (e.g., EGFR, VEGF, or PD-L1 pathways). However, cross-therapeutic cases (such as the evaluation of metformin, thalidomide, or anti-inflammatory compounds in cancer contexts) illustrate the growing translational permeability between oncology and other fields like endocrinology or immunology.
Overall, oncology exemplifies how repurposing has evolved from opportunistic reuse into a systematic strategy that capitalizes on established safety profiles, validated mechanisms, and well-defined regulatory pathways. Together, these trends position oncology as the epicenter of both de novo innovation and repurposing, highlighting the synergistic role of these two approaches in accelerating therapeutic progress against complex diseases.
Neurology/psychiatry
Psychiatry and neurology together rank second for de novo drug approvals, representing approximately 14% (186 out of 1336 total approvals), and hold a similarly strong position for repurposed drug approvals, accounting for approximately 13% (57 out of 451). According to our data, this sustained prominence reflects both the clinical urgency and the market potential associated with disorders of the central nervous system (CNS), encompassing neurodegenerative, neuropsychiatric, and cognitive conditions. The increasing prevalence of diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), major depressive disorder, and eating disorders (exacerbated by population aging and societal stressors) continues to drive innovation and investment in this field.
The high rate of de novo approvals in psychiatry and neurology is primarily driven by the pursuit of disease-modifying and symptomatic therapies, particularly for AD and PD, where unmet needs remain profound. Recent developments in amyloid-targeting antibodies and neuromodulatory agents illustrate a renewed optimism for mechanisms that may alter disease trajectories rather than merely alleviate symptoms. These scientific advances are reinforced by the FDA’s willingness to apply accelerated approval pathways to neurodegenerative and psychiatric indications when early biomarker evidence supports clinical potential.
Repurposing also plays a crucial and complementary role in this area, accounting for 15% of all repurposed approvals. This reflects the pharmacological versatility of CNS-active compounds, many of which act on neurotransmitter systems or neuroinflammatory pathways shared across multiple conditions. Drugs like amantadine, initially developed as an antiviral, are now used to manage dyskinesia and tremor in PD, while agents such as bupropion, repurposed from depression to smoking cessation, exemplify how cross-indication modulation of dopaminergic and noradrenergic systems can be therapeutically leveraged.
This dual trajectory (de novo innovation seeking transformative mechanisms and repurposing exploiting pharmacodynamic continuity) illustrates how the CNS field strategically combines scientific exploration with translational pragmatism. By accelerating access to safe and mechanistically validated molecules, repurposing mitigates the high attrition rates and R&D costs that have historically challenged drug development in psychiatry and neurology.
Cardiology
Cardiology represents one of the most enduring areas of pharmaceutical innovation, accounting for approximately 9% of all de novo approvals (121 out of 1,336) according to our data. This steady output reflects both the global burden of cardiovascular morbidity and the persistent need for therapies addressing hypertension, atherosclerosis, heart failure, and thromboembolic events. The success of de novo cardiovascular development has historically been underpinned by well-established clinical endpoints, large patient populations for trial recruitment, and predictable regulatory frameworks that favor incremental innovation (e.g., new formulations or improved safety profiles within existing pharmacological classes).
When considering repurposing, cardiovascular drugs maintain a strong representation, accounting for about 8% of all repurposed approvals (37 out of 451). This coherence between de novo and repurposing trends underscores the strategic continuity of innovation in cardiology. Repurposing efforts often build upon the pleiotropic and cross-systemic effects of agents such as statins, beta-blockers, and ACE inhibitors, which exhibit beneficial actions beyond their primary targets, including anti-inflammatory, anti-thrombotic, or endothelial-stabilizing properties. Such mechanistic versatility allows for the rapid extension of approved agents into adjacent indications, reducing development time and improving cost-effectiveness.
The cardiovascular field thus demonstrates how repurposing can complement de novo innovation within mature therapeutic markets. By optimizing well-characterized drug classes rather than relying solely on novel molecular entities, companies balance clinical impact with economic sustainability, sustaining progress in an area that remains central to global disease burden yet increasingly constrained by cost and competition.
Infectious diseases
According to our data, infectious diseases remain one of the major therapeutic areas for de novo innovation, representing approximately 13% of all FDA approvals (173 out of 1336). This strong presence underscores the continuous need for novel anti-infective agents to combat emerging pathogens and antimicrobial resistance. The peaks observed in 2020–2021 correlate with the COVID-19 pandemic, during which accelerated regulatory pathways enabled rapid approval of antivirals and vaccines in response to the global emergency. This responsiveness illustrates the reactive nature of infectious-disease innovation, often stimulated by public health crises and characterized by high-risk, time-sensitive development programs.
In contrast, repurposing plays a more limited role in this area, accounting for only 5.5% of all repurposed approvals (25 out of 451). The relatively low rate of successful repurposing reflects the pathogen-specific pharmacodynamics of anti-infective drugs, which constrain cross-indication applicability. Although several agents (such as remdesivir, initially developed for Ebola and later authorized for COVID-19) demonstrate the potential of emergency repurposing, most such examples remain transient or context-dependent, with few achieving permanent regulatory approval for new infectious indications. This asymmetry highlights the scientific and regulatory challenges of generalizing anti-infective activity across unrelated pathogens.
Overall, infectious diseases exemplify a therapeutic field where de novo discovery remains irreplaceable, as the need for molecular novelty and evolving resistance patterns limits the feasibility of sustained repurposing strategies.
Gastroenterology
According to our data, gastroenterology represents a small share of de novo FDA approvals, with 3.3% (45 out of 1336), and only a slightly higher proportion among repurposed drugs, at 4.7% (21 out of 451). This limited increase suggests that gastroenterology is not a major driver of repurposing activity, but rather a peripheral domain where repositioning occurs selectively, often when mechanistic parallels with other immune-mediated conditions justify translational extension.
The modest level of de novo output reflects the biological complexity of gastrointestinal disorders, driven by intertwined processes involving inflammation, microbiota imbalance, epithelial repair, and metabolic modulation. These multilayered mechanisms hinder first-in-class discovery and contribute to a pattern where therapeutic progress more often relies on redirecting existing pharmacological strategies than on sustaining a large endogenous innovation pipeline.
Repurposed drugs in this field typically originate from immune or inflammatory indications outside the gastrointestinal tract. Corticosteroids, mesalamine derivatives and systemic immunosuppressants remain the most recurrent examples, having been extended into Crohn’s disease and ulcerative colitis, where similar cytokine circuits regulate epithelial injury. This pattern illustrates a pragmatic form of repurposing: modest in scale, but clinically useful in contexts where mechanistic overlap is strong and unmet needs persist.
Industry dynamics
The healthcare innovation ecosystem consists of different stakeholders, with the most pertinent players involved in R&D being public-oriented organizations (academic institutions, research institutes and non-governmental organizations (NGOs)), and for-profit oriented small- and medium-sized entities (SMEs) or large companies, whether their specialty is developing biotechnology or pharmaceutical products. This section explores the roles and strategies of these stakeholders in bringing repurposed drugs to market, focusing on the differentiation of R&D timelines for in-house versus outbound repurposing, the organizations responsible for marketing originator drug rights and their strategies, changes in industry approaches over time, and therapeutic areas most targeted by repurposing efforts.
Average R&D time for drug repurposing
According to our data, the average time between a drug’s initial FDA approval and its subsequent approval for repurposing is approximately 7.2 years, with durations ranging from 0 to 39 years, depending on the type of repurposing strategy and the decade (Fig. 6). This is much shorter than the 12–15 years typically required to bring a novel drug targeting a first indication to market2,12. These findings are consistent with literature highlighting drug repurposing as a highly efficient strategy for reducing R&D timelines by up to 50% compared to de novo drug development8,18.
Fig. 6. Trends in the average approval duration of repurposed drugs based on company continuity (1985–2024).
This figure presents annual trends in the time elapsed between the approval of the originator product and the subsequent approval of its repurposed indication. Values are shown separately for cases in which the repurposed drug is approved by the same company as the originator and cases involving a different company. Three-year moving averages (MA) are included to smooth year-to-year variability. Early-decade cases (1985–1990) may exhibit shorter intervals due to dataset left truncation.
Repurposed drugs brought on the market by another (different) company than the originator company (outbound repurposing) can be the subject of licensing or transfer agreements (if the drug compound was still under regulatory protection). Likewise, they can be the result of R&D on publicly available compounds, so compounds that are no longer protected by patent rights or data exclusivity rights. Since we did not include the analysis of IP rights on the originator vs. the repurposed compounds (subject of follow-up research), we exclude statements on whether the repurposed drugs are subject to licensing agreements, transfer of ownership or based on publicly available information. However, the timing between the marketing of the originator drug and the repurposed drug already provides insight, since the period of exclusive rights is known. Companies that brought the original drug as well as the repurposed drug to market (same company) have an obvious advantage as they own all the data needed to advance faster.
However, to fully appreciate this efficiency, it is crucial to analyze how repurposing timelines have evolved over time and the factors influencing these trends, as illustrated in Fig. 6. Understanding these dynamics can provide valuable insights into optimizing repurposing strategies and addressing barriers that may still limit their broader implementation.
Evolution of repurposing timelines
In Fig. 6, we observe a clear trend in the average approval duration for repurposed drugs over the past three decades. In the early 1990s, the average time for repurposing approvals hovered around 2–5 years for both in-house (“Same Company”) and outbound (“Different Company”) cases. However, this duration steadily increased during the late 1990s and peaked between 2005 and 2015, with approval times reaching approximately 11–18 years in some cases. This increase could be attributed to rising regulatory requirements, more extensive clinical validation demands, and the overall complexity of drug development during that period18,19. Post-2015, the timelines have gradually stabilized, converging to an average of 5 years for in-house projects and 7.5 years for outbound projects, reflecting advancements in repurposing strategies and regulatory efficiency19.
The slight reduction and stabilization in repurposing timelines can largely be credited to technological advancements. Early methods relied heavily on serendipity and traditional trial-and-error approaches, which were time-consuming and resource-intensive18,20. Over the past two decades, the development of HTS has revolutionized the field, enabling rapid identification of new therapeutic targets21. More recently, the integration of AI, big data, and network-based drug discovery has further accelerated the process20. AI-driven algorithms, for instance, analyze vast datasets to identify potential drug-disease associations, while big data techniques utilize existing pharmacological and clinical data to prioritize candidates for repurposing22. These innovations have reduced the need for lengthy experimental phases, contributing to the observed reduction in average timelines.
In-house vs. outbound repurposing
A critical insight from Fig. 6 is the difference in timelines between in-house and outbound repurposing. Drugs repurposed by the same company take an average of 6 years to receive FDA approval, compared to 9.1 years for those outlicensed to a different company. This distinction highlights operational and regulatory inefficiencies associated with outbound R&D19. When a drug is transferred to a different company, delays often occur due to knowledge transfer challenges, additional regulatory scrutiny, and the need to validate pre-existing data under new ownership18,19. Moreover, the newcomer may need to establish its own development and commercialization strategy, further extending timelines19.
On the other hand, in-house repurposing benefits from streamlined processes, as the original developer already possesses comprehensive knowledge of the molecule, its safety and PK/PD profile, and prior clinical data18. Additionally, in-house teams have access to proprietary preclinical and clinical data, enabling faster decision-making and reducing redundancies in R&D23. These efficiencies likely explain why in-house repurposing achieves shorter average timelines compared to outlicensing.
Integration of repurposing timelines and industry evolution
The data in Figs. 6 and 7 suggest that companies have become more proficient in repurposing over time. While the period from 2005 to 2015 marked a challenging period with elongated timelines (ranging from 11 to 18 years, as reflected in earlier analysis), the subsequent decline and stabilization in approval durations demonstrate significant progress. Improvements in regulatory pathways, the adoption of advanced technologies, and strategic focus have contributed to this shift19.
Fig. 7. Classification and industry dynamics of the top 20 companies contributing to cumulative FDA-approved repurposed drugs (1985–2024).
Each marker represents at least one FDA-approved repurposed indication for a given company in a given year. The rows list the 20 companies with the highest cumulative number of repurposed approvals, and the x-axis shows the year of repurposed approval. Marker color indicates company type (blue, pharmaceutical; orange, biotechnology). Marker shape indicates the application pathway (circle, both NDA and BLA in that year; square, NDA only; diamond, BLA only). Marker size distinguishes company size in 2023 annual sales (large ≥10 billion USD; small <10 billion USD). Schering-Plow was merged with Merck & Co. in 2009.
Pharmaceutical companies now employ more hypothesis-driven approaches, leveraging advancements in omics technologies, machine learning, and computational biology to systematically identify repurposing opportunities18,23. Collaborations between academia, biotech firms, pharmaceutical companies, and regulatory agencies have also fostered an environment conducive to efficient drug development23. The average repurposing timeline of 7.2 years represents a balance between the inherent challenges of drug development and the efficiencies gained through repurposing. Unlike de novo development, repurposed drugs benefit from established safety profiles, reducing the need for early-stage toxicology studies18. However, clinical trials for new indications, regulatory reviews, and potential intellectual property (IP) challenges still require substantial time and resources 19.
For outbound repurposed drugs, additional delays arise from the complexities of knowledge transfer to a new company, as previously discussed19. These challenges highlight the critical role of in-house expertise and proprietary data in achieving shorter timelines, while also emphasizing the importance of continued innovation and collaboration across the healthcare ecosystem.
Types of organizations involved in marketing repurposed drugs
In the fast and ever-evolving field of drug R&D, both biotechnology and pharmaceutical companies play a crucial role in commercializing healthcare innovations; however, they are principally different. To distinguish between biotechnological and pharmaceutical firms, we use the Global Industry Classification Standard (GICS), a widely recognized scheme published by Morgan Stanley Capital International (MSCI) and Standard & Poor’s (S&P) and commonly referenced by financial analysts24. Further, we adopt the annual sales of the company as an approximate measure of firm size, i.e., firms with more than 10 billion US dollars annual sales as large size25. This classification is summarized in Table 1.
Table 1.
Global Industry Classification Standard (GICS)48
| Pharmaceutical companies (GICS 35202010) | Biotechnology companies (GICS 35201010) |
|---|---|
| Firms involved in the research, development, or production of pharmaceutical products, including veterinary medications. | Firms focused on genetic analysis and engineering, primarily engaged in the research, development, manufacturing, and marketing of biotechnology products. It includes firms that specialize in protein-based therapeutics for human diseases. |
Through a mapping of the companies that market the FDA-approved de novo drugs that served to develop and market one or multiple FDA-approved repurposed drugs between 1985 and 2024 (see Fig. 3), we visualize the top 20 leading repurposing companies contributing to 41.63% of all drugs approved in the US (1985–2024), with large companies accounting for 31% (554 drugs) and SMEs for 10.63% (190 drugs) of the total (n = 744) de novo and repurposed drug combined.
We find that most de novo drugs mapped in our database were marketed by top 20 leading repurposing companies (29.12%, 389 drugs out of a total 1336). These top companies are also major players in drug repurposing, responsible for 355 of the repurposed drugs out of the total 451 repurposed drugs. The correlation between a firm’s large number of de novo drug approvals and its extensive portfolio of approved repurposed drugs is an indication of the diversity of drug projects that companies pursue, including focusing on de novo drug development, as well as drug repurposing.
Among the 355 drugs repurposed by these top 20 companies, 64.7% (230 drugs) are originally marketed by them. It implies that big pharmaceutical companies conduct in-house R&D to repurpose existing products for new indications. The IP ownership on the compound (incl. its use to treat the original indication), together with the confidential data related to the initial indication clinical trials (incl. the safety data on the first-in-human use of the compound), provides them with a competitive advantage and creates a substantial barrier for third parties who wish to enter the drug repurposing market. These market exclusivity protections, including patents and data exclusivity on original drugs tested in clinical trials, make it hence utterly challenging for other companies to start researching compounds that are still under “a form of” protection 26.
Among major pharmaceutical companies, Eli Lilly continues to follow a sustained pattern of drug repurposing efforts. (Figs. 7 and 8). A notable example is the identification of baricitinib, owned by Eli Lilly, originally developed for rheumatoid arthritis, as a treatment for COVID-19. Leveraging computational methods, BenevolentAI, an AI-driven biotech company, collaborated with Eli Lilly and identified baricitinib as a potential inhibitor of viral entry pathways and inflammation associated with COVID-19. These AI-generated hypotheses complemented concurrent expert-driven evaluations of JAK inhibitors and other immunomodulators, which were already being clinically explored at the onset of the pandemic. This combined evidence ultimately supported FDA approval in 202227.
Fig. 8. De novo versus repurposed FDA-approved CDER drugs among the top 20 repurposing companies (1985–2024).
This figure compares, for each of the top 20 companies with the highest cumulative number of repurposed drug approvals, the total number of FDA-approved de novo drugs (blue bars) and repurposed drugs (orange bars) recorded between 1985 and 2024. Bars represent the number of CDER-approved products attributed to each company as the marketing authorization holder at the time of approval. The figure highlights heterogeneity in organizational strategies, with some companies showing balanced portfolios of de novo and repurposed drugs, while others rely more heavily on repurposing to expand therapeutic reach and extend product lifecycles.
Key factors driving Eli Lilly’s leadership in repurposing might include its vast repository of (pre-)clinical data, amassed through numerous drug approvals, and its strategic integration of AI technologies and collaborations. In 2008, Eli Lilly partnered with Entelos, utilizing the Metabolism PhysioLab platform to model diabetes and explore repurposing opportunities. By 2011, the company launched the Open Innovation Drug Discovery (OIDD) platform, targeting multidrug-resistant tuberculosis and other neglected tropical diseases, further expanding its focus on repurposing.
From 2019 onwards, Eli Lilly’s application of AI became increasingly measurable. In 2019, the company collaborated with Atomwise to integrate AI into early drug discovery, accelerating the identification of repurposing candidates. In 2021, it invested in MiNA Therapeutics, supporting RNA-activated therapies with potential applications across diverse conditions. This commitment to computational technologies was reinforced in 2022 through a partnership with Schrödinger, applying advanced modeling for drug discovery and repurposing28.
Eli Lilly’s sustained effort in drug repurposing is evident in Fig. 8, where it identifies 22 repurposed drugs, among the significant portfolios in the industry. This extensive activity reflects a long-term, consistent strategy and aligns closely with its broad investment in de novo drug development (32 new drugs, Fig. 8), underscoring the cumulative impact of its ongoing commitment. The company’s consistent involvement over decades is further evident in Fig. 7, which illustrates its enduring role in repurposing activities.
Dynamic pattern of companies involved in drug repurposing
Over the years, drug repurposing efforts have varied widely across companies (Figs. 7 and 8). Some firms have maintained consistent repurposing activities throughout the study period (1985–2024), e.g., Eli Lilly and Novartis AG, while others have approached repurposing more sporadically, e.g., UCB SA. This variability likely reflects differences in strategic priorities, internal capabilities related to IP, funding, human resources and Merger and Acquisitions(M&A).
Our findings indicate that a notable temporal gap exists between the initial repurposing efforts for NDAs and BLAs, with NDAs entering the repurposing landscape three years earlier. This delay can be attributed to the greater availability of FDA-approved NDAs before 2000, when their number was approximately sevenfold that of FDA-approved BLAs, a gap that has since narrowed. Repurposing activity remained heavily skewed toward NDAs throughout 2000–2010, reinforcing the view that small‑molecule repositioning delivers superior cost‑efficiency2. However, more recent data reveal a pronounced focus on BLA activity. In de novo approvals, biologics account for 164 of 622 (26.37%) after 2010, up from 94 of 714 entities (13.17%) before 2010. The change is even starker in repurposing approvals, where biologics represent 134 of 282 cases (47.5%) post-2010 compared with just 27 of 169 (16%) in the earlier period.
Furthermore, Schering-Plow Corporation entered the repurposing market as early as 1986, followed closely by Amgen Inc. and AstraZeneca Plc, which began as smaller players. Initially, repurposing was primarily undertaken by smaller pharmaceutical and biotechnology firms; however, as of 1996, the field saw an increasing presence of large pharmaceutical firms. These firms have shown sustained engagement, with an average of at least 20 years of repurposing activity.
Peaks in company participation were notably observed around 1997 and 2013, which align closely with major patent cliffs for blockbuster drugs in 2000 and 201129,30. In the late 1900s, pharmaceutical firms faced substantial revenue declines as patents expired on high-revenue products, such as Prozac by Eli Lilly and Claritin by Schering-Plow, between 2001 and 2002, with the Hatch-Waxman Act (1984) making generic drugs easier to enter. This prompted an increased urgency to identify alternative revenue streams compared to the exponentially increasing cost of developing entirely new drugs31. Similarly, the peak around 2013 reflects another wave of patent expirations, placing significant pressure on large pharmaceutical and biotech firms. The patents for several blockbuster drugs, including Lipitor and Caduet (both developed by Pfizer), expired in 2011. These two drugs, together with Combivir and Solodyn, accounted for over $7 billion in annual sales prior to patent expiration. Collectively, patent expirations for blockbuster drugs during this period placed an estimated $250 billion in global pharmaceutical sales at risk between 2011 and 201530. Many firms sought to mitigate the impact of generic competition by intensifying their focus on drug repurposing as a strategy, leveraging known compound data, incl. safety and PK/PD profile, and pre-existing supply chains. Advancements in computational biology and data-driven drug discovery, enabling companies to systematically screen large libraries of approved compounds for potential repurposing candidates, further accelerated this strategy32.
Mapping strategic therapeutic choices in drug repurposing
The Sankey diagram (Fig. 9), derived from our dataset of FDA-approved repurposed drugs, provides a visual representation of the directional pathways through which compounds originally approved for one therapeutic indication have been redeployed into other therapeutic areas. By mapping these transitions, the diagram captures both the intra-domain continuity of repurposing and the cross-therapeutic flows that define translational innovation.
Fig. 9. Sankey diagram mapping FDA-approved CDER drugs by original therapeutic area (Left) to the top 5 repurposed therapeutic areas (right).
This Sankey diagram visualizes the flow of FDA-approved drugs from their original therapeutic areas (left side) to the top five therapeutic areas into which they were subsequently repurposed (right side). Each stream represents the number of repurposed approval events linking an original indication to a new therapeutic domain. The diagram highlights predominant cross-domain transitions and illustrates how mechanistic generalizability often drives repurposing toward high-prevalence or high-value therapeutic areas.
According to our data, oncology and psychiatry/neurology dominate as both sources and targets of repurposing, reflecting the extensive mechanistic and clinical overlap within these fields and their central role in the broader pharmaceutical ecosystem. Beyond these intra-therapeutic patterns, distinct cross-domain connections emerge: for instance, endocrinology contributes to oncology through metabolic agents such as antidiabetics, while rheumatology serves as a source for dermatology and gastroenterology via immunomodulatory drugs initially designed for autoimmune conditions. These translation routes illustrate how repurposing frequently follows mechanistic continuity (for example, through pathways of angiogenesis, immune signaling, or inflammation) rather than purely opportunistic discovery.
The varying widths of the pathways in Fig. 9 reflect the relative frequency of these transitions, revealing that some therapeutic areas act as mechanistic hubs, exporting drugs to multiple related domains, whereas others remain largely self-contained. This visualization, therefore, offers a dynamic view of the strategic and biological landscape of drug repurposing, highlighting how scientific convergence, compound availability, and regulatory flexibility together shape the trajectory of modern pharmaceutical innovation.
Analysis of overall patterns
Oncology
According to our data, oncology emerges as the most prominent node in the Sankey diagram (Fig. 9), acting simultaneously as a dominant source and target of repurposing activity. The majority of these flows occur within the oncology domain itself, reflecting the extensive redeployment of antineoplastic agents across related tumor types that share underlying molecular drivers such as EGFR, VEGF, or PD-(L)1 signaling. This pattern illustrates the exceptional translational permeability of oncology, supported by a mature scientific ecosystem (characterized by validated molecular targets, robust biomarker frameworks, and regulatory instruments such as the FDA’s Accelerated Approval or Breakthrough Therapy designations) that collectively facilitate rapid adaptation of existing compounds to new malignancies. Such intra-domain extensions, however, raise important conceptual questions about the boundary between repurposing and incremental innovation. In this study, only cases involving distinct therapeutic or mechanistic shifts were classified as repurposing, whereas within-class or within-site tumor extensions were excluded and defined as label extensions (see Box 1 and Methods, “Inclusion criteria and classification”). The prominence of the Oncology → Oncology flow in the Sankey diagram thus visually represents the scale of internal diversification, even if many of these cases fall outside the strict regulatory definition of repurposing used in our dataset.
Beyond these intra-domain trajectories, oncology also serves as a significant source of cross-therapeutic innovation. Several FDA-approved drugs originally developed for hematologic or solid malignancies have been successfully repurposed in non-oncological conditions where immune modulation or vascular remodeling play a central role. A paradigmatic example is rituximab, an anti-CD20 monoclonal antibody first approved for non-Hodgkin lymphoma and later authorized for rheumatoid arthritis and pemphigus vulgaris. These extensions illustrate how oncology-derived immunotherapies can be redirected toward autoimmune or dermatological disorders driven by shared B-cell–mediated pathways. Similarly, anti-angiogenic strategies originally developed for cancer have inspired therapeutic translation into other vascular diseases, although ophthalmologic approvals, such as those for ranibizumab or aflibercept, typically rely on distinct molecules engineered for ocular specificity rather than label extensions of oncology drugs. This distinction underscores the methodological rigor required to separate pharmacological inspiration from regulatory repurposing.
Conversely, inflows into oncology from other therapeutic areas are far less frequent but equally revealing. Thalidomide remains a canonical example of a drug repurposed from an anti-inflammatory and dermatologic-infectious context (originally used for erythema nodosum leprosum) to multiple myeloma, where its immunomodulatory and anti-angiogenic properties provided a new therapeutic rationale that led to FDA approval in 2006. Endocrine and metabolic agents, such as metformin, represent another class of drugs extensively investigated for potential antitumor properties due to their influence on metabolic reprogramming and AMPK activation. However, despite numerous observational signals, the clinical evidence remains inconsistent, and benefits appear confined to subpopulations of cancer patients with coexisting metabolic disorders. As such, these agents remain in an exploratory phase rather than constituting confirmed regulatory repurposing cases, a distinction that aligns with our inclusion criteria and reflects the reviewers’ emphasis on definitional clarity.
Taken together, these findings confirm oncology’s central position in the repurposing ecosystem as both an exporter and importer of therapeutic innovation. Its dominance stems from the biological versatility of oncogenic pathways (angiogenesis, immune signaling, DNA damage response) that connect cancer with other pathophysiological systems. Yet, the asymmetry of its flows is equally instructive: while oncology readily donates mechanisms to immune-mediated and inflammatory diseases, it rarely imports them, reflecting both scientific selectivity and regulatory conservatism. This dual role positions oncology as a mechanistic hub in the modern repurposing landscape, where innovation increasingly propagates along shared biological axes rather than within rigid therapeutic boundaries.
Psychiatry and neurology
In the Sankey diagram (Fig. 9), psychiatry and neurology appear as a tightly connected node characterized by dense intra-domain flows and a limited but significant number of cross-therapeutic exchanges. The predominance of internal transitions reflects the deep pharmacological and mechanistic continuity that unites psychiatric, neurological, and pain-related disorders, where drugs modulating serotonergic, dopaminergic, or GABAergic systems can be readily redeployed across multiple CNS indications. Such within-domain recycling of molecular scaffolds explains why most flows converge between epilepsy, depression, anxiety, and neuropathic pain rather than extending into unrelated therapeutic territories.
A smaller number of cross-domain inflows and outflows nevertheless highlights the CNS’s permeability to systemic mechanisms. Inbound flows originate mainly from cardiology, where drugs like propranolol transitioned from cardiovascular to neuropsychiatric use, gaining FDA approval for anxiety and migraine prophylaxis. This transfer exemplifies how modulation of peripheral autonomic tone can acquire central therapeutic relevance when pathophysiological mechanisms overlap. Conversely, outbound flows extend toward pain and inflammatory pathways, supported by the immunomodulatory properties of certain antidepressants. For instance, amitriptyline and other tricyclic antidepressants (originally psychiatric agents) have long been used in chronic neuropathic pain, illustrating the translational reach of CNS-acting compounds beyond their primary domain.
The Sankey thus portrays psychiatry and neurology as a bidirectional but self-dominant hub: a domain that absorbs mechanistic inputs from other systems yet primarily recycles its own pharmacological repertoire. This structure underscores a central principle of the repurposing network (neural plasticity as pharmacological adaptability), where receptor cross-talk and shared neurotransmitter pathways facilitate translational reuse within the CNS while keeping cross-therapeutic flows relatively contained. In contrast to oncology, whose repurposing dynamics depend on molecular target modularity, the CNS relies on the functional redundancy of signaling systems to sustain internal innovation. Consequently, psychiatry and neurology emerge in the Sankey not as exporters of pharmacological classes, but as mechanistic consolidators, concentrating repurposing activity around a confined yet richly interconnected neurobiological core.
Cardiology
In the Sankey diagram (Fig. 9), cardiology occupies a distinctive position as a stabilizing axis within the repurposing network. Most of its flows are self-contained, indicating that cardiovascular innovation predominantly circulates within its own mechanistic ecosystem. This internal coherence reflects the highly conserved nature of cardiovascular pharmacology, where a limited set of biological targets (such as adrenergic signaling, calcium handling, and renin–angiotensin modulation) underpins a wide spectrum of conditions. These shared mechanisms enable efficient intra-domain repurposing, allowing molecules initially developed for hypertension, arrhythmia, or ischemic heart disease to be extended to adjacent indications without loss of mechanistic precision.
Beyond this internal translation, cardiology also generates cross-therapeutic flows toward a few select domains, most notably dermatology and oncology. The repurposing of propranolol from a cardiovascular to a dermatologic context represents a paradigmatic example: originally indicated for hypertension, it was later approved for infantile hemangioma, where its antiangiogenic and vasoconstrictive properties were leveraged to suppress vascular proliferation. Similarly, statins, while primarily lipid-lowering agents, have been repurposed or clinically explored in oncologic and inflammatory settings due to their pleiotropic effects on endothelial function, oxidative stress, and cytokine signaling. These examples illustrate that when cardiovascular drugs exit their native domain, they tend to do so along vascular or metabolic axes rather than through unrelated mechanistic routes.
The cardiology network thus appears both mechanistically cohesive and selectively expansive. Its dense intra-domain flows suggest a field optimized for incremental translation, where repurposing acts as a mechanism of clinical refinement rather than diversification. At the same time, its limited but meaningful cross-therapeutic exports demonstrate how well-characterized molecular frameworks (particularly those governing vascular tone and endothelial integrity) can underpin innovation beyond traditional cardiovascular boundaries. This dual behavior situates cardiology as a translational anchor in the repurposing landscape: a domain where mechanistic depth sustains internal continuity, yet whose pharmacological vocabulary remains sufficiently universal to influence other therapeutic fields.
Gastroenterology
In the Sankey diagram (Fig. 9), gastroenterology emerges as a convergent target node, receiving translational inputs from multiple domains (most prominently rheumatology, oncology, and endocrinology) while generating comparatively few outbound flows. This asymmetry underscores the integrative nature of gastrointestinal therapeutics, where inflammation, immune modulation, and metabolic regulation intersect, creating fertile ground for repurposing drugs initially conceived for systemic or autoimmune diseases.
The most prominent inflow originates from rheumatology, reflecting the shared immunopathological architecture of chronic inflammatory conditions. Anti-TNF-α agents such as infliximab and adalimumab, developed for rheumatoid arthritis, were subsequently repurposed for Crohn’s disease and ulcerative colitis, gaining FDA approval as some of the earliest examples of mechanism-based cross-domain repurposing. Similarly, IL-12/23 and IL-6 inhibitors followed analogous trajectories, illustrating how advances in rheumatology immunotherapy have systematically expanded the therapeutic armamentarium for inflammatory bowel disease.
A second major inflow derives from oncology, where drugs targeting angiogenesis and epithelial growth have been redeployed to gastrointestinal contexts that share aberrant vascular or proliferative mechanisms. Bevacizumab, originally approved for colorectal and other solid tumors, exemplifies this translational pathway, having informed treatment strategies for gastrointestinal stromal tumors and related neoplastic disorders. The gastrointestinal field thus absorbs oncologic mechanisms related to cell proliferation, angiogenesis, and immune evasion, translating them into chronic inflammatory or neoplastic contexts within the digestive system.
A more limited but mechanistically intriguing set of flows connects endocrinology to gastroenterology. Antidiabetic and metabolic drugs (particularly GLP-1 receptor agonizts) have influenced therapeutic approaches to nonalcoholic steatohepatitis (NASH) and obesity-associated gastrointestinal dysfunction, extending the metabolic logic of endocrinology into the digestive sphere. Although not all of these transitions correspond to formal FDA-approved repurposing events, they illustrate the metabolic continuum captured by Sankey’s Endocrinology → Gastroenterology connection.
Collectively, these cross-therapeutic flows depict gastroenterology as a mechanistic sink, drawing upon immunologic, oncologic, and metabolic advances to address diseases characterized by multifactorial pathophysiology. Its position within the Sankey network illustrates the translational permeability of gastrointestinal disorders, where immune and metabolic pathways converge to sustain repurposing potential. By integrating therapeutic innovations from neighboring domains rather than generating novel outflows, gastroenterology embodies a model of import-driven innovation, one that relies on cross-domain knowledge transfer to expand its therapeutic landscape.
Dermatology
In the Sankey diagram (Fig. 9), dermatology functions mainly as a receiver of cross-therapeutic flows from rheumatology, with secondary inputs from oncology and infectious diseases, while exporting selected immunotherapies toward gastroenterology and the respiratory axis. This configuration reflects the skin’s position as a peripheral interface of systemic immune activity, where cytokine networks (TNF-α, IL-12/23, IL-4/13, and B-cell signaling) converge.
The most substantial inflow stems from rheumatology, where biologics such as infliximab, adalimumab, and ustekinumab, originally developed for rheumatoid or psoriatic arthritis, were approved for plaque psoriasis. These transitions illustrate how shared cytokine pathways facilitate direct redeployment across tissues. Oncology-derived B-cell inhibitors provide a second, narrower inflow: rituximab, first used for non-Hodgkin lymphoma, later gained approval for pemphigus vulgaris, showing how anti-tumor immunotherapy can be redirected toward autoantibody-driven skin disease.
Infectious-disease inflows include ivermectin, repurposed from antiparasitic use to topical rosacea, and thalidomide, reintroduced for erythema nodosum leprosum, exemplifying immuno-infectious dermatologic repurposing. Outbound flows move along type-2 inflammation axes, as with dupilumab expanding from atopic dermatitis to asthma and nasal polyposis, and ustekinumab extending from psoriasis to Crohn’s disease and ulcerative colitis.
Overall, dermatology acts as a mechanistic junction, importing mature immunotherapies from neighboring domains and exporting validated cytokine-targeted strategies once efficacy and safety are demonstrated in the skin. This dual role highlights dermatology’s function as a translational bridge: a field that de-risks systemic immunology and accelerates repurposing along shared inflammatory pathways.
Discussion
Our results demonstrate that drug repurposing functions as a critical strategic lever, particularly during periods of financial strain, such as looming patent cliffs that pose substantial risks to revenue continuity. By extending the utility of existing compounds, companies can mitigate the impact of expiring patents and avoid the costly and time-consuming process of developing entirely new drugs. This strategy is evident in our dataset, where 70.26% of repurposed drugs marketed by leading firms stemmed from compounds they originally developed, highlighting a reliance on in-house R&D to sustain and enhance market position4. Large pharmaceutical companies, such as Pfizer, exemplify a broad-spectrum repurposing approach, targeting diverse therapeutic areas like oncology, neurology, and cardiology, thereby diversifying their portfolio and reducing dependency on single-product revenue streams. Conversely, firms like Genentech specialize in oncology, leveraging niche expertise to achieve sustained market influence in high-value domains 33,34.
This dichotomy in repurposing strategies has significant implications for collaborative networks. Companies adopting a specialization-focused approach, like Genentech, often deepen existing relationships with academic principal investigators (PIs) and research institutions, enabling the co-development of products within established networks35. For example, collaboration with academic oncology experts has allowed Genentech to streamline clinical development for niche cancer therapies, building on shared expertise and pre-existing partnerships35,36. In contrast, firms with a diversification strategy, such as Pfizer, increasingly pursue new collaborations to explore novel therapeutic areas and technologies. These partnerships often involve biotech startups or AI-driven drug discovery firms, enabling access to emerging computational tools and novel datasets that extend beyond their historical therapeutic focus 18,37.
Moreover, our data illustrates that repurposing frequently involves expanding into new therapeutic areas through cross-disciplinary approaches, necessitating networks that bridge academia, industry, and data science. Firms engaged in broad repurposing activities are more likely to establish new partnerships to address therapeutic needs outside their core expertise, reflecting a strategic openness to innovation and market adaptation38,39. These observations underscore that repurposing strategies (whether broad or niche) are intrinsically tied to how companies navigate and shape their collaborative ecosystems to meet evolving market and scientific challenges.
The capacity to align therapeutic strategies with market needs through repurposing provides firms with a robust mechanism to balance risk and innovation. Diversifying efforts across various therapeutic areas mitigates the risks associated with shifts in regulatory and market priorities, such as increased incentives for specific diseases under frameworks like the ODA or ODD, as well as emerging therapeutic demands driven by climate- or pollution-induced diseases37. This adaptability allows firms to capitalize on opportunities in underexplored or incentivized domains. Conversely, a focused approach in high-value fields such as oncology enables companies to leverage established pharmacological knowledge for targeted advancements and build further on the collaborations and networks already established. Such strategies deepen expertise while maximizing the value of existing partnerships and clinical data.
Our findings support existing literature, which emphasizes the role of repurposing in extending the lifecycle and market potential of drugs. For instance, Novartis’ engagement in oncology-driven repurposing showcases how firms can build resilience and address evolving patient needs by leveraging known compounds to meet chronic and complex disease challenges2. This case exemplifies how a focused repurposing strategy not only strengthens the firm’s presence in high-need therapeutic areas but also fosters collaboration within a specialized network of academic and clinical partners, enhancing innovation and maintaining competitive advantage.
The growing commercial success of repurposed drugs has heightened competition in the pharmaceutical industry. Products such as Ozempic®, Wegovy®, and Mounjaro® (originally developed for diabetes) have been repurposed and repositioned through successive regulatory approvals addressing distinct disease domains, unlocking multibillion-dollar markets40–42. This shift underscores the lucrative potential of repurposing, particularly in areas with overlapping patient populations and unmet medical needs. As clarified in Box 2, semaglutide (marketed as Ozempic® and Wegovy®) illustrates how a single active ingredient can follow multiple regulatory and therapeutic trajectories, ranging from incremental line extensions to genuine therapeutic repurposing and brand-level repositioning. By distinguishing these three levels, our classification framework ensures that only regulatory approvals reflecting a clear therapeutic shift across disease domains are captured as repurposing events. This methodological nuance is particularly important in the current competitive landscape, where the boundary between innovation and lifecycle management has become increasingly blurred.
As companies race to dominate these expanding markets, speed and innovation in repurposing pipelines have become critical competitive factors. Firms adopting AI-driven discovery models or forming partnerships with data-focused organizations have a clear advantage, as these strategies reduce development timelines and enhance targeting precision22,41,42. The competitive landscape also incentivizes firms to prioritize high-value therapeutic areas, with a notable focus on chronic diseases such as obesity and cardiovascular disorders. Leveraging an established pharmacological base allows large companies to scale production and marketing rapidly, while smaller firms and academic consortia must innovate collaboratively to remain competitive. Consequently, the interplay between competition and collaboration is now shaping the future of repurposing, with firms balancing speed-to-market with long-term sustainability and equitable access.
The rise of computational repurposing reflects a broader industry trend toward predictive, data-driven innovation, with leaders such as Eli Lilly demonstrating the integration of bioinformatics and AI into repurposing pipelines41. Our findings indicate a shift from opportunistic to systematic repurposing, where AI-driven algorithms assess cross-disease potential as part of the drug lifecycle. This evolution suggests that computational approaches will increasingly complement traditional discovery methods, contributing to more targeted and efficient hypothesis generation.
While computational tools have accelerated the identification of repurposing hypotheses, the translation of AI-generated predictions into clinically validated therapies remains nascent. The case of baricitinib illustrates how AI can complement, rather than replace, expert-driven and necessity-based approaches to drug selection during health crises. JAK inhibitors, including baricitinib, were rapidly prioritized for COVID-19 treatment through both data-driven insights and independent clinical reasoning, underscoring the potential (but also the current limits) of AI-enabled repurposing.
In this evolving landscape, the application of AI in repurposing offers a predictive framework in which in silico tools can identify and prioritize candidate drugs for novel indications based on molecular, pharmacokinetic, and clinical data42. The establishment of robust machine learning models that can accurately predict efficacy across indications could further reduce discovery timelines and increase success rates, positioning computational repurposing as an emerging R&D competency with transformative potential for future drug development.
The COVID-19 pandemic underscored the utility of repurposing as a rapid-response strategy to address public health emergencies. Drugs like remdesivir, initially approved for Ebola, were swiftly repurposed to treat COVID-19, demonstrating the adaptability of repurposing in high-stakes contexts17. Regulatory adaptations, such as Emergency Use Authorizations (EUAs), provided an expedited pathway for repurposed drugs, suggesting a framework that could extend to routine care in high-need therapeutic areas43. For example, conditional approvals could fast-track access to therapies in areas of chronic or rare diseases, where traditional regulatory timelines often hinder timely access to treatments.
This potential to introduce “conditional approvals” for repurposed drugs represents a transformative shift in regulatory frameworks. It would provide a pathway to embed repurposing into routine R&D and patient care, facilitating the delivery of potentially life-saving therapies under a dynamic approval model. Broadening regulatory pathways to accommodate repurposing as an incentive for increased industrial investment could optimize drug availability, particularly in areas where unmet needs persist, thereby enhancing both crisis preparedness and therapeutic reach.
Intellectual property (IP) barriers continue to constrain repurposing, particularly for drugs that remain under patent protection. However, models such as the Orphan Drug Designation (ODD) for rare diseases illustrate how collaborative frameworks can incentivize repurposing in areas of high unmet medical need23. Our results reveal that repurposed drugs are most concentrated in therapeutic areas such as oncology, psychiatry/neurology, and cardiology, where mechanistic generalizability and established regulatory pathways facilitate translation across indications. By contrast, rare and genetic disorders remain underrepresented, underscoring the need for collaborative and open innovation frameworks to address therapeutic areas where commercial incentives are limited4.
There are currently many multi-stakeholder initiatives being established, in most instances driven by governments and public institutions, such as the Horizon Europe programs RePo4EU and the SIMPATHIC Consortium. These initiatives aim to create large-scale infrastructures for mechanism-based drug repurposing and data sharing across Europe.
In parallel, public–private partnerships (PPPs) such as RARE-NL bring together public and private stakeholders, along with patient organizations, to co-create, promote knowledge exchange, and foster sustainable business models that increase the accessibility of repurposed drugs for patients with rare diseases.
The continued development of PPPs, shared databases, and repurposing consortia can further alleviate IP-related challenges, enabling companies and public institutions to collaborate on repurposing initiatives while preserving competitive advantages. In therapeutic areas with relaxed IP restrictions or strong public health priorities (such as rare diseases and infectious conditions), repurposing as a collaborative model can enhance industry responsiveness to unmet medical needs, maximizing collective expertise and resources44.
Conclusions
As demonstrated by our findings, drug repurposing holds substantial potential as a central pillar in pharmaceutical R&D. This study analyzed the repurposed drugs that stemmed from previous FDA-approved drugs. It would be incredibly valuable to further include the lessons learned from drug repurposing efforts that failed, either in the preclinical or the different clinical studies. Additionally, including the current use of off-label repurposed drugs in future analyses. In this regard, still many efforts are needed to overcome the regulatory and financial barriers that still exist to bring affordable repurposed drugs to the patient45.
The analysis did not reveal FDA-approved drugs being brought to market directly by public or not-for-profit entities, although these actors play a critical role in the ecosystem of drug repurposing. Notable examples include the Best Pharmaceuticals for Children Act (BPCA) program in the US, under which the National Institutes of Health (NIH) may act as a “sponsor of last resort” to conduct studies and enable product label updates for pediatric and neonatal uses, including several cases of successful repurposing46. Another emblematic case is nitisinone for alkaptonuria, where sustained patient-advocacy engagement was pivotal in launching the pivotal study and securing eventual EMA approval for this rare metabolic disease47. This example underscores both the transformative role of patient-led initiatives in driving repurposing and the need to reconsider regulatory frameworks that remain predominantly sponsor-centric.
Also, in addition to grant funding for drug repurposing, exploring new funding mechanisms, such as Social Impact Bonds (SIBs), that support not-for-profit actors to repurpose off-patent drugs and generic medicines (which are generally less profitable for pharmaceutical companies) could accelerate the number of repurposed drugs that could be tested in independent clinical trials45.
Further, to fully unlock the potential of drug repurposing, future work must address critical gaps in standardization, collaboration, and affordability. Developing standardized predictive frameworks for repurposing involves creating unified methodologies and tools to systematically evaluate the potential of drugs for alternative therapeutic uses. These frameworks would integrate AI-driven analytics, such as machine learning algorithms capable of analyzing molecular structures, drug-target interactions, and disease pathways, alongside advanced computational modeling. By leveraging extensive datasets, including real-world evidence, clinical trial outcomes, and genomic information, these systems can identify promising cross-therapeutic applications at the early stages of drug development. Such standardization would not only harmonize approaches across stakeholders, but also provide consistent criteria for assessing drug repurposing opportunities, thereby reducing discovery times and enhancing success rates43. These frameworks should prioritize addressing diseases with unmet needs while ensuring timely and equitable access to therapies.
Expanding repurposing efforts into gene and cell therapies, particularly Advanced Therapy Medicinal Products (ATMPs) regulated by CBER, presents an untapped opportunity. These therapies align with the industry’s ongoing shift toward precision health, where personalized medicine becomes the norm34. For example, AI-assisted identification of gene-editing targets could enable the repurposing of existing CRISPR-based tools, thereby bridging gaps between innovative platforms and rare disease treatments.
A pressing concern raised by physicians and healthcare providers involves the significant price hikes often associated with repurposed drugs following FDA approval for new indications. These increases can severely limit patient access, particularly for rare diseases. For instance, deflazacort, initially a low-cost corticosteroid used internationally, was repurposed for Duchenne muscular dystrophy (DMD) and saw its price rise from approximately $1000 annually to $89,000: a 7300% increase after FDA approval. Similarly, pyrimethamine (Daraprim), repurposed for toxoplasmosis, experienced a notorious price jump from $13.50 to $750 per tablet, igniting widespread backlash over barriers to treatment. Other drugs highlight similar trends: lanreotide, repurposed for rare neuroendocrine tumors, saw a marked price increase upon approval for its new indication, leveraging orphan-drug market exclusivity. Ixabepilone, initially used for advanced breast cancer, and bupropion hydrochloride, repurposed from depression to smoking cessation, also demonstrated substantial post-repurposing price increases.
While these cases illustrate legitimate concerns about affordability, it is equally important to recognize that repurposing often entails extensive redeployment of resources, including new clinical trials, pharmacovigilance programs, and regulatory submissions that can represent up to 90% of the total investment required for an NME once indirect costs are accounted for. Consequently, moderate price adjustments may reflect the need to recover these costs and sustain innovation. However, excessive mark-ups risk undermining public trust and limiting access, particularly in orphan and pediatric indications where few therapeutic alternatives exist.
These contrasting dynamics highlight the urgent need for comprehensive analyses of post-repurposing pricing models to differentiate justified redevelopment costs from speculative pricing behaviors, and to design policies that ensure both innovation sustainability and affordability for patients. Addressing these challenges requires rethinking pricing models and fostering stronger collaboration between governments, payers, and manufacturers. Transparency in the pricing process must be prioritized, coupled with incentives for keeping repurposed drugs affordable. Policymakers should explore innovative pricing and reimbursement frameworks to balance industry profitability with the public health imperative of accessibility. Furthermore, targeted reforms, such as pricing caps for orphan drugs or expanded compulsory licensing provisions, could ensure affordability without discouraging innovation.
Ultimately, ensuring the accessibility of repurposed drugs is critical to realizing the full potential of drug repurposing as a strategy to meet unmet medical needs efficiently. Without structural changes, the promise of repurposing could be undermined by its unintended consequences for healthcare equity and affordability.
Building a predictive, collaborative, and adaptable drug repurposing ecosystem will require stronger partnerships between pharmaceutical companies, biotech startups, academic institutions, and public agencies. These collaborations can combine resources, expertise, and datasets to enable systematic repurposing efforts, fostering innovation while ensuring accessibility. A cohesive framework would allow stakeholders to identify promising compounds efficiently, address unmet therapeutic needs, and maximize the value of existing molecules.
In parallel, regulatory support is crucial to streamline approval pathways for repurposed drugs without compromising safety and efficacy standards. Simplifying these pathways, alongside policies that encourage investment in repurposing efforts, can help reduce barriers associated with IP and market exclusivity. Furthermore, creating incentives that balance profitability with public health priorities (such as regulatory flexibility or targeted funding for clinical trials) can make repurposing an attractive option for all stakeholders.
An optimized ecosystem would elevate drug repurposing from a secondary strategy to a primary driver of pharmaceutical innovation, aligning it with patient-centric therapeutic development. By addressing challenges such as affordability, collaboration, and predictive accuracy, the industry can establish a more responsive, equitable, and efficient system. Such a system would not only meet existing therapeutic needs but also adapt to emerging health crises, providing timely and accessible solutions for patients worldwide.
Supplementary information
Description of the additional supplementary file
Acknowledgments
Not applicable
Author contributions
Conceptualization: S.A. and H.S.; Methodology: S.A. and X.N.; Data curation: S.A.; Formal analysis: S.A., X.N., and B.S.; Investigation: S.A.; Supervision: H.S.; Writing—riginal draft: S.A.; Writing—review and editing: S.A., X.N., B.S., and H.S.
Peer review
Peer review information
Communications Medicine thanks Hermann Am Mucke and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Data availability
All data used in this study were generated by the authors through systematic extraction from FDA primary sources. Drugs@FDA is an online public database that provides access to FDA approval documents, product labels and regulatory histories and can be accessed at https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases. The FDA Approved Drug Products database, commonly referred to as the Orange Book, is also publicly available online at https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm. The aggregated numerical data used to generate the figures in this article are provided in Supplementary Data 1. The complete curated dataset developed for this study is protected under an i-Depot registration and cannot be publicly disseminated due to intellectual property restrictions and ongoing research use. However, all methodological steps required to reproduce the dataset are fully described in the article and the supplementary materials, allowing reconstruction of the dataset from publicly accessible FDA sources.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
The online version contains supplementary material available at 10.1038/s43856-025-01344-1.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Description of the additional supplementary file
Data Availability Statement
All data used in this study were generated by the authors through systematic extraction from FDA primary sources. Drugs@FDA is an online public database that provides access to FDA approval documents, product labels and regulatory histories and can be accessed at https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases. The FDA Approved Drug Products database, commonly referred to as the Orange Book, is also publicly available online at https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm. The aggregated numerical data used to generate the figures in this article are provided in Supplementary Data 1. The complete curated dataset developed for this study is protected under an i-Depot registration and cannot be publicly disseminated due to intellectual property restrictions and ongoing research use. However, all methodological steps required to reproduce the dataset are fully described in the article and the supplementary materials, allowing reconstruction of the dataset from publicly accessible FDA sources.