A custom collaboration with: Quintiles
Tuning Up the Tools
Improving the efficiency of the pharmaceuticals business depends on more than just a business model. It also relies on how these businesses use the tools that are available (see “The J&J Way”).
When asked what tools can advance healthcare technology, Peer Staehler, chief scientific officer at febit, a synthetic-gene company in Heidelberg, Germany, says, “We need to fully exploit the genome. We know it contains the code of life; let’s take this fact seriously!” He adds, “Molecular biology tools can be used for disease detection, prevention and therapy monitoring. We already know that blood-borne nucleic acids are highly informative for dozens of disease states, yet their use is still in its infancy.” As an example, Staehler mentions that cancers include molecular fingerprints, which could be exploited to create more effective therapies.
Successful pharmaceutical companies will also find new ways to use traditional genomics knowledge. “The conversation about human health is shifting from a debate on nature versus nurture to a more nuanced discussion about how both nature and nurture affect the trajectory of disease,” says Nathan D. Lakey, president and chief executive officer at Orion Genomics in St. Louis, Mo. “Clearly, nature—or the sequence of As, Ts, Gs and Cs that make up our genetic code—plays a principal role in determining who will develop disease. However, environmental factors have been shown to alter the epigenetic signature, which is a second code written on top of the DNA sequence that regulates gene expression.” Such changes in expression can trigger disease. “Research is yielding critical insights into how epigenetic signatures influence the start and progression of diseases like cancer, developmental disorders and diabetes,” Lakey explains This knowledge is also being turned into medical tools. As Lakey notes, “Epigenetic tests in development promise to predict risk of future disease, offering doctors and patients the opportunity to take preventative action. In the near future, clinicians will more effectively treat disease by targeting therapy to patients’ genetic and epigenetic profiles using epigenetic biomarkers.”
Beyond simply finding more ways to use genetics of any sort, companies should look for tools that determine technology’s potential at earlier stages of development. In some cases, the best tools can arise from a combination of old and new. In an e-mail interview, Arthur Sands and Brian Zambrowicz—chief executive officer and chief scientific officer, respectively, at Lexicon Pharmaceuticals in The Woodlands, Texas—write: “For example, researchers started using lab mice decades ago. Since mice and humans share about 99 percent of the genes considered to impact health, this animal remains a useful model for many diseases. To make this tool even more useful, mice can be combined with genetic engineering to create knockout mice—mice in which a specific gene has been inactivated.”
They continue: “A knockout mouse can be used to model how a drug will work before it is even invented. Since most drugs work by inhibiting a particular target—for example, an enzyme—a gene knockout is the equivalent of a drug that completely inhibits its target.” Consequently, knockout mice can give pharmaceutical researchers a head start on unraveling how a drug will work, as well as what side effects might occur.
“Over the past several years,” write Sands and Zambrowicz, “Lexicon has used this powerful technology to discover over 100 biologically validated targets, and currently has four compounds in phase 2 clinical development— demonstrating that knockout mice are indeed a good tool for developing novel drugs for human disease.” So, tools like this could make pharmaceutical companies more efficient at finding new drugs.
Other experts also encourage pharmaceutical companies to find ways to reduce the failure rates of drugs by turning to more advanced technology. For example, Kevin Hrusovsky, chief executive officer at Caliper Life Sciences in Hopkinton, Mass., says, “Given that one of the greatest drains on pharma R&D is the cost of clinical failure, it is imperative to ensure that in vitro and preclinical in vivo data are predictive of the clinical outcome.” He sees a range of ways to accomplish that. “An abundance of recent technological developments, such as next-generation sequencing, genomic/proteomic biomarker discovery, companion diagnostics and in vivo imaging with new modalities have strengthened the bridge between in vitro and in vivo research efforts, thereby facilitating more clinically relevant drug development,” he says.
Moreover, Hrusovsky sees technology as a potentially economical solution. “The good news is that the current cost of enabling tools, both in terms of capital equipment and labor, has reached an attractive price point that renders this a compelling value proposition,” he says. “Given the long timeline and high cost of drug development compared with the relatively modest cost of these technologies, the benefit of being able to make swift decisions at critical junctures is a simple yet tangible way of improving the return on investment.”
The process of developing therapeutics has multiple expense points, which will undoubtedly change as new business models replace old ones. Here is a snapshot of the current major expenditures related to the bench-to-bedside enterprise.
© 2010 Scientific American,
a division of Nature America, Inc.
All Rights Reserved.