Innovating Lifecycle Management with Data-Driven and Enabling Technologies

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Pharmaceutical companies are developing new strategies to address the ever-increasing development costs for new drug therapies and maximize the value of their existing drug portfolio.

Repurposing existing compounds of an approved drug for better performance, patient convenience, or new indications, or using a new delivery route or combination therapies are now central to lifecycle management strategies. It is estimated that the development costs for repurposing a drug total approximately $300 million and takes six and a half years (1), compared with an approximate cost of $2.6 billion over 10 years or more to bring a new drug to market. According to a recent report from FDA, in 2017, 14 drugs were approved for a new indication, four for new patient populations, 14 products with new formulations, and four new dosage forms of existing medicines (2).

Drug repurposing is, to a large extent, driven by bioinformatics, which help identify new indications and special populations that would benefit from the treatment. This trend is especially important as people live longer, and the focus of healthcare shifts to managing life-threatening and complex diseases that manifest in older people and for which effective therapies are still lagging. Many drugs can act on multiple disease targets but are only being used for the treatment of one specific disease in a given formulation. For example, nelfinavir was launched as a protease inhibitor for the treatment of human immunodeficiency virus (HIV) but was later found to target the mammalian mechanistic target of rapamycin (mTOR) pathway, helping to overcome proteasome inhibitor resistance in multiple myeloma patients (3). As innovations such as digitalization, miniaturization, biotechnology, and advanced manufacturing continue to pave the way for science and technology to gain knowledge and capabilities in healthcare, repurposing and redesigning medicines will remain an effective strategy for the medical world to increase R&D efficiency and better serve the needs of patients.

New approach to drug repurposing

The old approach for drug repurposing was mainly based on clinical observations and off-label use in non-approved indications. The new approach is increasingly driven by data and enabled by computational and experimental methods integrating pharmacologic, genomic, phenotypic, and clinical data systematically collected from various sources (e.g., genome-wide association studies [GWAS]). These advancements in clinical science provide better understanding of the multifactorial nature of the complex diseases and the need for simultaneous treatment to multiple clinical targets. Recently, a public database for the repositioning of drugs was launched that intends to systematically collect and compare all data of approved and failed drugs as well as their indications and make these data publicly available (4). 

The therapeutic target and the required dose of repurposed drugs might be very different from the originally developed drug product. For example, digitoxin used in the treatment of heart failure and arrhythmia shows cytotoxic effects on different cancer cells at a much lower plasma concentration (5). The US National Institutes of Health (NIH) has established the National Center for Advancing Translational Sciences (NCATS) to stimulate the screening of approved drugs for other disease targets and, if identified, to support the clinical trials and regulatory process (6). 

Finding new treatments for cancer and age-related diseases

The major disease area for which redesign of approved drugs is most often investigated is for the treatment of the different types of cancer and, interestingly, for the prevention of aging processes. Due to the important role of bioinformatics in the discovery of drugs that are appropriate for repurposing, it is not surprising that a complex disease field such as oncology is a primary target for drug repurposing. Bioinformatics contribute to the discovery of disease mechanisms in which multiple cellular and molecular variations are involved. As a result, evidence is provided on the synergistic effects of targeting multiple clinical variations to achieve the desired clinical outcomes. Once the clinical targets are identified, the drug libraries can be screened systematically to find existing molecules acting on these targets. Thalidomide, for example, was originally launched as a sedative and hypnotic in the late 1950s but withdrawn from the market due to serious adverse reactions. It was later found to be an effective inhibitor of the tumor necrosis factor alpha (TNF-ɑ) and neovascularization in tumor tissue and is being repurposed in combination with ixazomib and dexamethasone for the treatment of multiple myeloma.  

The discovery of medicines that prevent aging is stemming from the increasing life expectancy and observations that patients treated with certain drugs experience a slower aging process. Some of these drugs have been confirmed in animal models to reduce the risk in certain age-related diseases and are subsequently being used or investigated for delayed aging in humans. For example, rapamycin is being used to prevent organ rejection after transplantation and has shown additional effects for veterinary as well as human use as a therapeutic agent. A derivative of rapamycin has been shown to reduce the decline of immune functions in healthy older people. Similar results have been observed with metformin. Metformin shows a dose-dependent improvement of metabolic health and life-span in mice and is being investigated for heart failure protection in dogs. The compound has achieved substantial attention for reducing the risk for cancer, cardiovascular diseases, and overall mortality of diabetic patients (7). To provide the clinical evidence for the claims, the American Federation for Aging Research (AFAR) has initialized the Target Aging with Metformin (TAME) study to evaluate the effect of metformin on aging and age-related diseases (8).    

Repurposing by formulation

There is a growing awareness of the increasing age and multimorbidity of the older population leading to patients with a high disease and therapeutic burden. In addition, there is a demand for treatment options of pediatric patients that are not appropriately served by existing standard pharmaceutical products. Inappropriate medication altering-for example, by tablet-crushing to administer the drug to patients with swallowing issues or through enteral feeding tubes-put patients at risk for adverse outcomes. There is evidence that in care homes, the incidence for patients affected is approximately one-third (9). 

Many drugs for pediatric patients have to be compounded, which can be quite challenging even for an experienced hospital pharmacist, especially for drugs with a bad taste. This issue has triggered many new regulations requiring the development of pediatric and geriatric formulations beyond the standard tablets for the adult population. In this context, existing and approved drug products are, therefore, being reformulated for underserved patient populations by respective drug delivery and dosage-form design. This trend will become even more pronounced, when considering the increasing role of genetic and phenotypic data as well as advanced diagnostics and digital health technologies leading to personalized drug combinations and individual dosing regimens (10). In fact, the need for effective pediatric formulations has been recognized with Pediatric Research Equity Act (PREA) and other regulations requiring pediatric studies of new drugs. 



Many existing drugs can be “repurposed” in a new formulation to serve a variety of different subpopulations within a specific disease or disease cluster, especially when these drugs were launched as a tablet in a few dose strengths and several years of clinical experience has been gained. Recognizing this need, the regulatory authorities have, as a result, put in place meaningful regulations to encourage the industry to develop enhanced formulation or fixed-dose combinations (FDC). Azithromycin is a good example of reformulation to enable a drug’s use in the pediatric patient population using the 505(b)(2) regulatory pathway. The antibiotic drug has to be administered by body weight and is applied to very young children up to the very old. Because the originally launched solid dose forms of the product were not suitable for the required subdosing, extended-release and taste-masked microspheres were developed that are administered as a suspension, allowing administration of the drug at all doses and to patients with limited swallowing capabilities, including young children and older patients with dysphagia. 

Effective treatment of many diseases depends on the patient-specific selection of two or more drugs to be taken simultaneously. FDCs require a high degree of dosing flexibility of each individual drug, which can be obtained by multiparticulate formulation. Multiparticulate technology also provides a platform for immediate as well as targeted drug release, enabling different drug-specific release patterns within the FDC product. Recently published data have shown that 145 drug products were approved by FDA between 1980 and 2012, whereby 28 involved at least two new chemical entities (NCE) and 117 were composed of only one NCE. For the latter, the patent exclusivity was increased by nine years on average. FDA approved, on average, 1.2 FDC per year in the 1980s and seven FDCs between 2010 and 2012, showing the increasing importance of simplifying the complex treatment schedules to better serve patients (11).     

Leveraging enabling technologies to address solubility and bioavailability challenges 

One of the major challenges with drug repurposing is the potential lack of return of investment (ROI). Clinical trials require high financial investments and even repurposed drugs with a known pharmacological and safety profile may not reach the desired clinical end-point. Such investments are justified if the new product is sufficiently protected against off-label use of the existing generic versions of a drug. 

To prevent the pharmaceutical ecosystem from limiting access to the innovative therapies made available through drug repurposing, advances in science and technology in drug product design should be considered. Given that repurposed drugs are based on rather “old” products, new dose strengths, drug-delivery technologies, and dosage forms might play an important role in achieving the new therapeutic claims and preventing off-label use in drug repurposing. Through advanced drug delivery and product design, additional benefit can be built into the product, such as site-specific delivery or bioenhancement, to increase the efficacy, safety (e.g., reduce adverse drug reactions), and/or effectiveness (e.g., adherence).

Itraconazole, for example, is under investigation for the treatment of prostate cancer at a higher dose of 600 mg/day (12). Itraconazole, developed in the early 1990s as an oral dosage form, has poor aqueous solubility and shows a non-linear pharmacokinetic and a food effect, which leads to high inter- and intra-subject variability. According to FDA labeling, the absolute bioavailability of the market product is approximately 55%. The labeling also points out the dose-dependent drug absorption as well as the influence the gastric pH, for example, by co-administration of proton pump inhibitors on drug absorption (13). Using advanced drug-delivery science in drug repurposing of itraconazole provides an opportunity to improve the bioavailability and reduce its variability and dosing frequency. 

Thalidomide is being repurposed in combination with other drugs for several types of cancer. Thalidomide has a poor aqueous solubility and is investigated in the different clinical trials in dose ranges of 50–200 mg/day. Thalidomide is reported to have linear and similar pharmacokinetic profiles across different patient populations, but no consensus is reached on the absolute bioavailability (14). The importance of the formulation was recently shown in a bioequivalence study in fed and fasted conditions. The comparison of an immediate-release capsule and tablet formulation showed different pharmacokinetic profiles (15), suggesting that thalidomide can be targeted to achieve better clinical outcomes by formulation. Since most of the co-administered drugs that are being used in the clinical studies with thalidomide are oral products (e.g., gefitinib, ixazomib, dexamethasone, tegafur uracil, irinotecan, and acetylsalicylic acid) (16), FDC formulations provide another opportunity for the repurposing of thalidomide. This is especially true for patients with a high disease and therapeutic burden, as FDC products reduce the therapeutic complexity for the patient.


While the risks and costs in drug discovery and development continue to increase, the huge amount of knowledge systematically collected and analyzed by computational methods has become an important source for discovering new indications for existing or failed drugs as well as the importance of targeting multiple biologic pathways to effectively treat a disease. In addition, there is growing awareness that there are patient populations with special needs that are not yet addressed by standard drug products, contributing to medication errors and poor therapeutic outcomes. Repurposing of drugs and formulations is a relatively low-risk and increasingly attractive investment. Moreover, some of the repurposed drugs target non-classified diseases, which are gaining substantial interest due to increasing life expectancy and demographic shifts. 

The key to success requires a multidisciplinary approach involving the different stakeholders in healthcare, including the patient, to identify the true needs of both healthcare professionals and patients and how they can be served via drug repurposing and reformulation. It is also crucial to fully understand the range of enabling technologies available and where to apply them to meet the often-complex target product profiles of patient-centric medicines. Flexible technology platforms and dosage forms, including solubility enhancement and multiparticulates, continue to find increased application in improving and repositioning existing drugs, as well as achieving the desired therapeutic outcomes in doing so. 


  1. N. Nosengo, Nature534, 314-16 (2016).
  2. FDA, Advancing Health Through Innovation: 2017 New Drug Therapy Approvals,, accessed May 22, 2018.
  3. C Driessen et al., Haematologica101, 346-355 (2016).
  4. A.S. Brown, C.J. Patel, Scientific Data, 4:170029, published online Mar. 14, 2017, doi: 10.1038/sdata.2017.29.

About the author: Sven Stegemann, PhD, is director, Pharmaceutical Business Development, Lonza Pharma & Biotech, Rijksweg 11, B–2880 Bornem, Belgium,