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The Personal Challenge
Any pharmaceutical company using any business model must aim for making medicine more personal and individualized. The tantalizing prospect of optimizing medical outcomes by tailoring drugs and therapies to match features in each individual’s unique genetic makeup and environmental profile drives the buzz surrounding personalized medicine. “The idea is to develop drugs that work for selected individuals and reduce adverse events, and to charge a premium for them, knowing that they appeal to payers because overall they save money,” says Edward Abrahams, executive director of the Personalized Medicine Coalition, a non-profit consortium of drug and biotech companies, patient groups and research organizations in Washington, D.C.
But for personalized medicine to achieve its potential (including 11 percent annual growth to $452 billion by 2015, according to PricewaterhouseCoopers), large pharmaceutical companies will need to cast aside their old model of developing blockbuster drugs and adopt a more collaborative approach that focuses on developing specialized therapies for patients who carry biomarkers or genetic variants indicating risks for diseases such as breast and colorectal cancer, diabetes, macular degeneration and other conditions.
Doing so will require the development of more powerful genome-scanning technologies and companion diagnostic tests to determine whether a particular drug or therapy will help (or harm) a specific patient. Currently, however, other than the largest drug companies, most pharmaceutical companies are wary of incorporating biomarkers and companion diagnostics into clinical trials for fear they will increase costs and delay drug development. According to a recent McKinsey & Company survey, the average drug company is developing companion diagnostics for fewer than 10 percent of its compounds, despite clear urgings from the government to do so across the board.
The Food and Drug Administration already requires companion diagnostic tests before prescriptions are written for several drugs, including Pfizer’s Selzentry (maraviroc) for HIV, and Genentech and Roche’s Herceptin (trastuzumab) for breast cancer. In Europe, the European Medicines Agency requires companion diagnostics for about a dozen drugs, among them, Novartis’s Tasigna (nilotinib) for leukemia and GlaxoSmithKline’s Ziagen (abacavir) for HIV/AIDS.
Many large pharmaceutical companies are developing their own diagnostics divisions and merging or collaborating with established companies. Roche is already a diagnostic market leader with a 20 percent share of the in vitro equipment market. Last July, GlaxoSmithKline (GSK) and Abbott Laboratories announced they would develop a companion diagnostic for GSK’s MAGE-A3, an antigen-specific cancer immunotherapeutic drug under development. In February, Pfizer and DxS Diagnostics similarly declared they would develop a companion diagnostic for an immunotherapy vaccine in development for the treatment of glioblastoma multiforme.
Despite all of this work, no firm has yet determined a timeline for successive stages in the drift to smaller populations treatable by single drugs. The issue doesn’t call for an immediate one-shot solution. “You’re not going to get down to one patient–one drug for a long time, if ever,” says Wayne Rosenkrans, chairman and president of the Personalized Medicine Coalition. “It’s going to happen in stages.” Initially, pharmaceutical companies might develop drugs that effectively treat, say, a third or a quarter of patients with specific conditions. Improved understanding of the genetics of disease will then open up opportunities for drugs targeted at smaller and smaller groups of patients. Advanced knowledge of other physiological systems, such as the immune system, will also play a role in new treatments (see “Immunological Patriots”).
The stratification process has already started in some cases. Phase 3 clinical trials of Iressa—an AstraZeneca drug targeting a gene overexpressed in small lung tumors—showed that patients with a particular mutation responded to the drug, whereas others didn’t. Approval of the drug thus contains the proviso that it should be administered only to those patients who will respond to it. That approach applies “not just to lung cancer, or just cancer,” says Raju Kucherlapati, professor of genetics at Harvard Medical School. “It’s true for other diseases.”
But that is only a start. “Tailored therapy today is directed at relatively large populations of 10,000 to several million,” says Jerry Kinzel, vice president of bioproduct research/development at Eli Lilly. “The challenge will come when it’s truly individualized: creating new reagents for each individual.”
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.
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