The average cost of clinical trials has increased threefold over the last 12 years, with a new drug estimated to require investment of around $802 million to bring to market. Significant capital is lost through investment in drug candidates that fail late-stage clinical trials and do not reach the market. Trials take between seven and 12 years to complete, resulting in a considerable time lag before profits are realized. There are also concerns over patent expiry, because a patent lasts only 20 years and the marketable life of a drug could be reduced by more than 50% before it achieves regulatory approval. Thus, there is a massive drive across the pharmaceutical industry to find innovative methods to identify potentially unsuccessful candidates as early as possible and improve the efficiency of clinical trials.
Industry participants are investing in skills and techniques to quantify changes in a patient’s biomarker patterns after the administration of an experimental drug. These changes may be chemical, genomic, or proteomic and can indicate a drug’s safety and efficacy in human subjects.
The key benefit of biomarkers in clinical trials is that they can be used to eliminate unsuccessful drug candidates very early in the clinical trial process. Biomarkers are currently used in-house to make a “go/no-go” decision to decide whether to take a compound into the clinical phase. This may involve computer modeling and preclinical animal testing to identify a drug that is ineffective or has toxicological effects.
The ultimate goal is to use panels of biomarkers as validated surrogate end points as a substitute to conventional physiological measurements, which require frequent hospital visits and expenditure on trial management staff. The discovery of biomarkers specific to certain drugs will also provide a simple efficacy test for use with the marketed product in the future.
However, this goal is still a long way off, and several problems must be solved before biomarker discovery can make savings in drug development. For example, there is a preconception that biomarker tests are unreliable and are only effective measurements in specific populations, but the hope is that this preconception can only be diminished as scientific knowledge expands.
There is also a lack of regulatory framework, which causes confusion among scientists. Regulatory agencies are aware that biomarkers can be used to improve clinical trial efficiency, but cannot compromise drug safety and efficacy to do so. They are, therefore, being cautious about implementing new regulations. However, the US Food and Drug Administration is actively promoting voluntary submission of biomarker data so that adequate case law can be published to encourage the validation of biomarkers as surrogate end points.
Biomarker discovery now receives heavy investment from major pharmaceutical firms and is generating new opportunities in contract research. The overall market for biomarker related products and services is currently estimated to be worth $639 million, and is anticipated to expand to $2.9 billion by 2008 at a compound annual growth rate of 28.5%.
The biggest drive across the industry is in the field of oncology. Cancer indications do not necessarily manifest themselves as easily measurable symptoms, and biomarkers could have tremendous application in drug efficacy testing. Clinical trials in oncology are also the most expensive to conduct owing to costs incurred through patient reimbursement for life threatening conditions, as well as human resources costs for conducting a wide range of tests over a long time period.
Although biomarkers will eventually reduce clinical trial cost and time, initial investment will be required. Adding a biomarker discovery program will increase the complexity of trials while biomarkers are discovered. Therefore, an entire industry is emerging in contract research services for companies lacking the required facilities and expertise for identifying biomarkers.
Biomarkers ultimately have the potential to reduce the cost and duration of clinical trials, but significant investment and effort into discovery and validation programs will be required before this potential is realized. The application of biomarkers is likely to expand when conclusive regulatory legislation is published, allowing their use as validated surrogate end points in clinical trials.
Filed Under: Drug Discovery