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Putting an end to an innovation crisis, the reality of which is the subject of debate, recent pharmaceutical innovations, the result of a combination of scientific, industrial, financial, political and economic reasons, lead to a diversification of products and to a strong interest of pharmaceutical companies for the so-called "niche" products (targeted therapies, rare diseases, etc.). These new molecules are put on the market at much higher prices than in the past. In the absence of reliable information on the costs borne by manufacturers, and knowing that high levels of margins have been observed, these prices raise legitimate questions. These are also motivated by the lack of relationship between the price and the therapeutic benefit of these new molecules. In France, faced with levels of expenditure likely to weaken the financial sustainability of the social protection system, the public authorities have so far always favored interventions on prices or the conditions and volume of reimbursement, in accordance with the existing regulation. Other regulations (use of the statutory license, group purchase, etc.) could in the future be used in a growing concern for the efficiency of public expenditure. The difficulties encountered in regulating a deeply transformed industrial sector call for a reform of national evaluation and regulation systems., (© 2018 médecine/sciences – Inserm.)

The cost of pharmacotherapy is increasing in the health care budget. The pharmaceutical industry is facing the exhaustion of medications that are largely prescribed and have a high profitability (blockbusters). Because of patient heterogeneity, there is a great interindividual variability of the responses to drug therapy. Thus, it is essential to better detect potential <> to avoid waste of resources resulting from the prescription of expensive drugs to poor responders. The development of personalized medicine, or precision medicine, certainly offers opportunities to the pharmaceutical industry, but also exposes it to new big challenges.

The identification of complete networks of protein-protein interactions (PPI) within a cell has contributed to major breakthroughs in understanding biological pathways, host-pathogen interactions and cancer development. As a consequence, PPI have emerged as a new class of promising therapeutic targets. However, they are still considered as a challenging class of targets for drug discovery programs. Recent successes have allowed the characterization of structural and physicochemical properties of protein-protein interfaces leading to a better understanding of how they can be disrupted with small molecule compounds. In addition, characterization of the profiles of PPI inhibitors has allowed the development of PPI-focused libraries. In this review, we present the current efforts at developing chemical libraries dedicated to these innovative targets., (© 2015 médecine/sciences – Inserm.)

Despite continued increase in global Pharma R & D expenditure, the number of innovative drugs obtaining market approval has declined since 1994. The pharmaceutical industry is now entering a crucial juncture where increasing rates of attrition in clinical drug development as well as increasing development timelines are impacted by external factors such as intense regulatory pricing and safety pressures, increasing sales erosion due to generics, as well as exponential increases in the costs of bringing a drug to market. Despite these difficulties, numerous opportunities exist such as multiple unmet medical needs, the increasing incidence of certain diseases such as Alzheimer's disease, cancer, diabetes and obesity due to demographic changes, as well as the emergence of evolving markets such as China, India, and Eastern Europe. Consequently, Pharma is now responding to this challenge by improving both the productivity and the innovation in its drug discovery and development pipelines. In this regard, the advent of new technologies and expertise such as genomics, proteomics, structural biology, and molecular informatics in an integrated systems biology approach also provides a powerful opportunity for Pharma to address some of these difficulties. The key features behind this new strategy imply a discovery process based on an improved understanding of the molecular mechanism of diseases and drugs, translational research that places the patient at the center of the research process, and the application of biomarkers throughout the discovery and development phases. Moreover, new paradigms are required to improve target validation and develop more predictive cellular and animal models of human pathologies, a greater capacity in informatics-based analysis, and, consequently, a greater access to the vast sources of accumulating biological data and its integrated analysis. In the present review, we will address some of these issues and in particular emphasize how the application of biomarkers could potentially lead to improved productivity, quality, and innovation in drug discovery and ultimately better and safer medicines with improved therapeutic efficacy in specific pathologies for targeted patients.