Drug discovery goes back to school: changing ecosystem of drug discovery and the rising role of academia (2014)

The last century has seen substantial resources dedicated to translating basic science discoveries into new medications. The majority of these initiatives have been driven by the pharmaceutical industry. This ecosystem is, however, changing. There is a growing awareness and involvement from the National Institutes of Health (NIH) and academic institutions, as well as a rising role for public–private partnerships. The pharmaceutical industry has faced a considerable challenge the last dozen years. The cost of bringing a new drug to market has expanded exponentially. Data from Scannell et al. show that the number of new drugs approved by the US Food and Drug Administration (FDA) per billion US dollars spent on R&D has halved roughly every 9 years. This is a decline of over 50-fold in inflation-adjusted terms. These data were derived from the 2011 Pharmaceutical Research and Manufacturers of America (PhRMA) Annual Survey (Scannell et al., 2012). Data also suggest that approximately $130 billion of patented sales will face replacement with generics by the year 2016. This “patent cliff” will impact 57% of the overall 2010 US sales. To address these concerns, the pharmaceutical industry has started to consolidate. Over the last couple of years, there has been a loss of more than 100,000 jobs and there continues to be efforts to reduce the workforce further. The pharmaceutical industry has also begun to decrease its internal research efforts, which provide an opportunity for innovation and different models for early drug discovery. Fortunately, as the pharmaceutical industry has been reducing its efforts in early drug discovery, there has been a simultaneous increase in the NIH's involvement in drug discovery and translation science. The NIH Roadmap has facilitated preclinical discovery and development through a variety of initiatives such as the Clinical and Translational Science Awards (CTSA), Molecular Libraries Program, Cures Acceleration Network (CAN), and the Bridging Interventional Development Gaps (BrIDGs), previously the NIH Rapid Access to Intervention Development (RAID) program (NIH: Roadmap, 2004; NIH: Clinical and Translational Science Awards Program, 2008; NIH: RAID, 2011; NIH: Cures Acceleration Network, 2014; NIH, Molecular Libraries Program, 2014). Another resource, the National Center for Advancing Translational Sciences (NCATS), is the newest of the 27 Institutes and Centers at the NIH (NIH: NCATS, 2014). Established in December 2011, this center is intended to focus on what is common across disease states and the translational process and collaborations among government, academia, industry, and nonprofit patient organizations. Projects may include catalyzing public–private translational research opportunities, repurposing drugs, rare disease therapeutics, and re-engineering translational sciences. Perhaps an indicator of the importance of these efforts is that although the NIH budget has been flat for the last couple of years, the NCATS budget in 2014 has increased by 14%. From the academic perspective, there has been a significant rise in the number of academic drug discovery centers. The Academic Drug Discovery Consortium (http://www.addconsortium.org/) reports that there are 103 academic drug discovery centers that are operational in the United States (ADDC, 2012). Not only is academia increasing their investment in drug discovery and translational science, but also there is an increase in the amount of academia–industrial partnerships. It is important to note that these are not just a particular pharmaceutical company being interested in the work of one professor at a university. The new alliances are broad based and utilize a brand new program format. These collaborations can build upon the strengths of both academia and industry. A 2011 survey of 78 small-molecule drug discovery centers sited within universities or nonprofit research organizations from across the United States revealed where the expertise for development or innovation lay. The academic centers appeared to excel in disease biology expertise and innovation, and to be better aligned with societal goals. The pharmaceutical industry was perceived to be much stronger in assay development, screening, and medicinal chemistry. This data show that both academia and industry have their respective strengths. The potential of bringing them together has merit as new innovation models are developed (Frye et al., 2011). Among academia's strengths is the ability to have a longer term focus and an unparalleled depth of knowledge on specific diseases. There are professors who have spent their whole life studying a specific target or a specific disease. Industry has to react to and sometimes has to change directions because of market pressure. Academia also has a greater climate of creativity and innovation accompanied by enhanced clinical interactions. Physician scientists who are treating patients in the same field that they are also researching bring a really novel and different perspective to the development process. Academia also has access to new biology and new tools and animal models; this provides some distinct advantages for doing academic drug discovery. Some of the challenges facing academia are funding and the current reward process. In academia, one is rewarded for being an independent scientist who focuses on hypothesis-driven scholarly research. Drug discovery is really more team-oriented and focused on product development. The pressure to publish also complicates drug discovery within an academic setting. Publications, which are paramount in academia, may compromise patent strategies. In addition, the chemical libraries that academics have access to for screening are not as diverse or as proprietary as those found in industry. An example of an academic drug discovery team that is actively collaborating with industry is the Hopkins' Brain Science Institute (BSi) (Johns Hopkins, 2007). Established in 2007 with a philanthropic pledge of $100 million, the Institute's mission is one of basic science to solve fundamental questions about brain development and function and also translational to use these basic science insights to develop novel small-molecule therapeutics for neurological and psychiatric diseases. In 2009, a Baltimore-based company called MGI Pharma was acquired by Eisai. A year later, in 2010 an entire research team moved from MGI Pharma to Hopkins. The new direction for the team was to work collaboratively with the faculty to translate the basic science discoveries into clinical therapeutics. The existing Hopkins faculty had expertise in identifying novel targets and in running clinical trials. The integrated team from industry had expertise in drug discovery, particularly in medicinal chemistry, assay development and screening, in vivo animal pharmacology/toxicology and drug metabolism, and pharmacokinetics. So the two groups complement each other. The team is currently engaged in half a dozen new drug discovery projects in collaboration with various Hopkins' basic science faculty. In 2011, the Hopkins' drug discovery team entered into a unique high-throughput screening collaboration with Eisai. The Hopkins team identifies new therapeutic targets that may be druggable and develops high-throughput screening assays for those targets. The Eisai team takes those assays and screens them against their own large proprietary drug library. The hits are identified and sent back to Hopkins, where the drug discovery team works to develop a clinical candidate focused on the screening hits. Eisai then has first rights to license that clinical candidate for commercialization. This is a very collaborative effort and a win-win situation for both sides. The academic center trying to do drug discovery does not have access to a large, diverse, drug-like library, and the pharmaceutical company does not have access to a lot of novel targets. So this collaboration provides both. In conclusion, the US drug discovery ecosystem has changed dramatically over the last dozen years. The business challenges facing the pharmaceutical industry have led to decreases in their internal efforts in early research. Meanwhile, academia and NIH are increasing their efforts in drug translation. There has been a very significant rise in both the number and sophistication of academic drug discovery centers, as well as public and private partnerships focused on translational research.