Editorial [Hot Topic: De-risking the Discovery and Development of New Drugs from Bench to Clinic (Guest Editor: Sergey Ilyin)]

The biopharmaceutical industry is facing challenges from increased generic competition, regulatory changes and other factors negatively impacting pharma economics. Industry is also presented with opportunities for improving overall research & development and business efficiency via de-risking development of novel drug candidates. Approaches to improve efficiency and decrease risk include in vitro and in vivo ADME (absorption, distribution, metabolism and excretion), biomarker-enabled development strategies, intelligent clinical trial design and overall risk management. ADME strategies to select and optimize drug candidates can significantly reduce PK-based failures in clinical trials, and more successfully predict drug-drug interaction potentials in the clinic. ADME strategies are reviewed in this issue by Balani et al. (Millenium Pharmaceuticals, Inc.). Biomarker approaches can facilitate transition between discovery, experimental medicine and full development and in some cases be a part of postmarketing activities. Biomarker methodologies include genomics, pharmacogenomics, proteomics, integrative strategies and molecular imaging. Pharmacogenomics and its role in discovery and development are discussed by Johnson et al. from Pfizer Global Research and Development. Integrative strategies, such as Functional Informatics, could incorporate several different technologies to cross validate findings. Genomics, proteomics and integrative strategies as they can be applied to clinical oncology biomarker discovery are reviewed by Belkowski and colleagues from the Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Noninvasive techniques are generally based on imaging modalities and include light imaging, CT, MRI, PET as well as different combinations of these modalities, for example PET/CT. Although all of these technologies can facilitate preclinical and clinical activities, it is beyond this issue to cover them in detail. PET provides an opportunity to non-invasively evaluate in vivo PK, receptor occupancy and pharmacodynamics (PD), and PK/PD, and could lead to a better prediction of dosing to be used in the clinic as well as to a reduction in the cost and duration of phase II clinical trials. It could also provide information to enhance our understanding of the mechanism(s) of action. PET technology provides an ability to complement with assays of therapeutic efficacy and potential adverse events. In diseases that are difficult to approach with traditional methods, PET will accelerate and improve compound development. PET technology is reviewed in this issue by Wang and Maurer from the Alza Corporation. Selection of the right dosing is of paramount importance for informed go/no go decision in clinical development. Of equal importance is a well-conceived overall design of a clinical study. This is of particular importance to trials with high placebo response rate and Yang, Cusin, and Fava from the Depression Clinical and Research Program at the Massachusetts General Hospital discuss various strategies to address this problem in antidepressant trials. Finally, Martin Mackay and his co-authors from Pfizer talk about overall strategies (technology, organizational, etc.) to handle risk in drug discovery and development. This issue is comprised of well referenced up-to-date edited manuscripts from leaders in the pharmaceutical industry and academia.