The potential of metabolomics, a systems approach to biochemical pathway analysis, to yield scientific and commercial benefits to healthcare and biotechnology enterprises is increasingly recognised.
Clinical drug development is moving into an era where high technology new diagnostics are key to the development of the majority of new drugs.
The current challenges facing drug discovery and development in terms of attrition are well documented. This article discusses how molecular imaging approaches from bench to bedside can not only streamline drug development, but also open up new opportunities in the treatment management of targeted therapies.
The mission at The University of Texas MD Anderson Cancer is to eradicate cancer, which remains a major cause of mortality worldwide. It is the second leading cause of death in the United States and globally, claiming more lives than malaria, HIV/AIDs and tuberculosis combined (or ~1 of every 7 deaths) (1-3).
Changing demands in global healthcare over the past 15 years have led to greater complexity and spiralling costs in drug development. The average price tag of taking a new drug from discovery to completion of Phase III clinical trials is now $2.87 billion (1), which means informed decisions need to be made early on about which compounds to pursue.
Next-Generation Sequencing (NGS) is moving quickly from early research into the regulated domains of drug development, diagnostic development, and clinical decision-making.
A silo mentality is an issue for any organisation, but it is particularly problematic for the pharmaceutical industry. Drug development is a multidisciplinary endeavour that relies on the cumulative efforts of highly skilled teams in order to be successful. Yet these teams cannot work in isolation.
The recent approval of the first liquid biopsy test for the diagnosis of non-small cell lung cancer (NSCLC) demonstrates how biomarker-based detection tools are becoming important components of precision medicine-based drug treatment regimes.
Magnetic Resonance Imaging (MRI) can be used to provide quantitative measurements in the form of imaging biomarkers. These measurements have a number of attractive characteristics: They are non-invasive, can provide organ and lesion localisation of morphology, physiology and metabolism and can be repeated over time.
The outlook for the drug industry continues to remain bleak in context of productivity and success rates. In spite of ongoing increase in R&D expenses and technology revolutions in the genomics and proteomics area, nearly 95% of drug programmes which enter clinical development fail.
Gamma scintigraphy is a non-invasive technique with applications in the development of drug products and the assessment of pharmacodynamic effects in humans. It enables the assessment of critical performance parameters that in vitro techniques attempt, but often fail, to predict. Quantification of pharmacodynamic effects (eg gastrointestinal transit; gall bladder emptying; lung mucociliary clearance) provides insights into the mode of action of drug candidates.
Over the last 10 years we have seen the introduction of several new 'ophthalmology only' pharmaceutical products emerge such as Trusopt (dorzolamide, Merck) and Xalatan (latanoprost, Pharmacia). Innovative products such as these have driven much of the ophthalmic pharmaceutical growth, outpacing the older products that were often developed for ophthalmology via other therapeutic areas.With the ophthalmic pharmaceutical sector currently at around $5 billion worldwide, the continued growth is likely to be driven by even more first-in-class entries in ophthalmology.Two areas that are especially poised for explosive growth are dry eye and retinal disease, in which many new therapeutic approaches are currently in development.
The key in vivo drug metabolism and pharmacokinetic studies continue to be undertaken using radiolabelled versions of drug molecules. Traditionally, the preparation of these isotopically labelled compounds was largely the domain of specialist internal radiochemistry groups within large pharmaceutical companies (Big Pharma).
Toxicological safety testing of compounds has not yet advanced to the point where measurement of gene expression is being incorporated in the internal decision process of most companies, much less the FDA approval process. The FDA has asked for voluntary submissions, is preparing guidelines for gene expression data and has identified surrogate biomarker assays as the avenue to escape the dilemma highlighted in the FDA white paper �Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products
The completion of the human genome project has focused tremendous interest in determining the structure and function of the tens of thousands of proteins that the genome encodes. Current structural determination techniques are difficult, time-consuming and not generally applicable to all proteins.
Biomarkers continue to become increasingly relevant in research and healthcare applications, as evidenced by the global market for products involved in their identification, validation, and use estimated at $8.3 billion in 2007 and projected to increase to $15 billion in 2010.
To have real business impact within preclinical drug development, Enterprise ELNs (Electronic Laboratory Notebooks) must provide a secure, scalable and searchable data management backbone across all disciplines focused on development of both small and large molecules, in compliant and non-compliant environments.
The effort to develop drugs that interact with the human immune system (whether by accident or design) has been dogged by a mismatch between the data derived from animal models (mice in particular) and that found in man.
With few exceptions, all compounds being submitted to the Food and Drug Administration (FDA) for approval in the United States will require an assessment of QT prolongation, either by a standard Thorough QT/QTc study, or a similar study modified to fit the safety profile of the compound and indicated patient population.