Beyond Blockbusters

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-01-01-2007, Volume 0, Issue 0

While not a panacea, pharmacogenomics is still a valuable trial tool that can make the recruitment process more efficient and eliminate the high costs associated with late-stage product failure.

In 2001, when news about the human genome was first published, much speculation ensued about the impact it would have on new therapies and treatments. One area that drew a significant amount of attention was pharmacogenomics, especially as it related to what many described as a revolution in drug development and commercialization: Personalized medicine.

Michael Murphy

While significant advances have been made in the field of pharmacogenomics over the past five years, detractors are quick to point out that not all of its initial promises have materialized. Unmet expectations have been a result of the field's inherent limitations, as well as inaccurate information regarding possible applications of pharmacogenomics-related technology.

Next revolution in medicine?

The study of an individual's genetic profile to better predict the toxicity, safety, and efficacy of drugs was first heralded as the next revolution in medicine due to its potential to help the pharmaceutical industry redefine the blockbuster model. At the core of this model is the assumption that a single compound can treat most patients suffering from a particular condition. However, at best most drugs are only effective in about 60% of the population.

The advent of pharmacogenomics led several analysts and members of the media to conclude that personalized medicine was the answer to this inherent flaw in the blockbuster model. At first, many believed that pharmaceutical companies would develop dozens of tailor-made formulations designed to match patients' genetic codes. However, research has shown that drug response is typically associated with fewer than four to six different phenotypes. Using pharmacogenomics to develop a large number of drugs targeting the same condition would not only be impractical from a cost perspective, but it would also be unnecessary.

Another challenge the industry is facing with regard to the blockbuster model is the escalating cost of drug development. The constant dollar amount to develop a new drug increased 5.8 times between the 1970s and 1990s. In addition, only 9% of drug candidates ever reach an NDA filing. It has become increasingly difficult for companies to justify the high costs and risks associated with developing a new blockbuster drug.

Pharmacogenomics has helped the pharmaceutical industry tackle this challenge in three basic ways: by facilitating the elimination of unfavorable drug candidates at earlier stages of development; by enabling companies to design clinical trials that more definitively prove drug efficacy; and by providing researchers with genomic data that can be used to rescue some drugs from failed clinical trials.

Focus on safety

According to a PriceWaterhouseCoopers1 report, 58% of drugs that failed during development were terminated because of efficacy or safety issues. Today, more pharmaceutical companies are using pharmacogenomics to recruit responders for clinical trials and to eliminate subsets of patients whose phenotype makes them likely to suffer from adverse reactions. Trial sponsors are now able to obtain more specific results using smaller patient populations and avoid the high cost of product failure later in the clinical testing process.

Some pharmaceutical companies have also started to see the benefit of using pharmacogenomics to demonstrate a drug's efficacy on a specific subset of patients. This process, called "enrichment" by the FDA,2 has the potential to rescue some drugs that fail in clinical trials. Enrichment strategies work to the extent that an underlying pharmacogenomic trait is really responsible for some patients responding, while others do not. We have to keep in mind that disease, age, sex, lifestyle, and race also play a part in drug efficacy.

Today we know that personalized medicine will never completely replace blockbuster drugs. Simply put, not all therapies are a good match for pharmacogenomics. The human genome has provided us with a roadmap. It has taken the industry a few years to realize that knowing the roadmap does not mean we know exactly what path each patient will travel.

Michael Murphy, President and CEO, Gentris Corporation

References

1. PriceWaterhouseCoopers, Personalized Medicine: The Emerging Pharmacogenomics Revolution (February 2005).

2. L.J. Lesko and J. Woodcock, Pharmacogenomics J, 2 (1) 20–24 (2002).