Meeting Report

For many years, the return on R&D investment in the pharmaceutical and biotechnology industries has been high, leading investors to expect consistent growth and encouraging researchers to pursue risky and expensive drug development projects. But the U.S. Food and Drug Administration (FDA) approved only 19 new drugs in 2007, compared with a peak of 60 new products in 1996. At the same time, $160 billion is invested in healthcare research globally each year. What accounts for the huge discrepancy in investment input and new drug output?

Alan Smith, executive vice president and chief scientific officer of the biotechnology company Genzyme, pointed to these figures as evidence of the challenges drug developers face during an October 7, 2008, panel discussion organized by the New York Academy of Sciences' Science Alliance for Students and Postdocs. (An archived version of the webcast can be found above.) Representatives from biotech, the pharmaceutical industry, the consulting industry, the FDA, and the National Institutes of Health (NIH), met to discuss the current landscape of the biotechnology and pharmaceutical industries, and what might lie ahead.

Robert Copeland, executive vice president and chief scientific officer of EpiZyme, and Cole Werble, editor-in-chief of The RPM Report, a publication that analyzes the effect of regulatory agency decisions on the pharmaceutical industry, argued that the R&D pipeline is full but the bar for getting new drugs approved has been set so high that few drugs can make it over. Meanwhile, the FDA is less likely to approve drugs that make incremental advances on an existing drug unless the new drugs are proven to be extremely safe, Werble said.

But Barbara Mittleman of the Office of Science Policy Analysis at the National Institutes of Health pointed out that the switch from pursuing drugs for acute diseases to the development of drugs for chronic diseases has changed the game. Because these drugs must be taken for years, perhaps for the rest of a person's life, determining their long-term safety is both critical and extremely challenging.

Smith noted another change that has made drug discovery more difficult. In the past, researchers focused on developing what he called replacement drugs, treating diseases caused by missing proteins or other factors by supplying a substitute. This approach is relatively straightforward and has a high success rate. Now researchers are working on interventional drugs—starting with an observation that a molecule has interesting biology and is implicated in various diseases, and ultimately trying to determine whether affecting that molecule's activity in humans would be useful. It is enormously expensive and extremely tough to go from in vitro and animal studies to humans because the former aren't good predictors of success in the latter, said Smith.

Looking ahead

Andrew Marshall of Nature Biotechnology and moderator of the symposium asked the panelists for insights into how the industry will adapt. The panelists agreed that no single strategy would solve all the new challenges. There is a trend toward tackling 'niche' diseases rather than looking for the next blockbuster drug, said Werble. Within an indication, biomarkers may be used to segregate populations, increasing the likelihood that a drug will be effective (by leaving out most people it won't work on) and decreasing the safety risk (by excluding people who wouldn't benefit from the drug but would have been exposed to the risks), said Smith. Thus, although the cost of development may be high, the value of the drug would also increase.

Patient stratification may also be used to obtain orphan drug designation under the Orphan Drug Act of 1983, which gives incentives aimed at promoting development of drugs for rare diseases. The designation may be given if drug companies can convincingly show that a subgroup of less than 200,000 people would benefit from the drug, said Peter Vaccari of the FDA's Orphan Drug Program.

"We need to completely rethink how we get the first data in humans that will tell us these drugs are worth pursuing."

But these measures may not be enough. "The drug discovery enterprise worldwide as presently configured and presently financed is unsustainable," declared Smith. "We need to completely rethink how we get the first bit of data in humans that will tell us that these drugs are worth pursuing," he argued, because in vitro and animal studies can be misleading and billions of dollars are lost subsequently on failures. The problem is that doing less early research increases the risk to the first people exposed to a drug, he said.

A number of innovations may make early tests more reflective of a drug's activity in humans, from transgenic mice with humanized immune systems and human organs to disease-specific cell lines, Marshall noted. The scientific community will no doubt test all of these systems, but it remains to be seen if they will be efficacious. Similarly, genomics, proteomics, and other widely touted techniques all play a role in drug development but none stands out as the key to finding new treatments quickly and at lower cost.

More government intervention?

High drug prices have caught the attention of all sectors of society, with many urging the government, as purchaser of about 35% of prescription drugs in the United States, to fight for lower prices. In the UK, an agency called National Institute for Clinical Excellence (NICE) evaluates not only if drugs work, but also the value of the drug and whether it is worth covering it under the National Health Service, Smith said. In the U.S., the Centers for Medicare & Medicaid Services plays that role to some extent, but currently there is no agency charged with carrying out comparative effectiveness testing and recommending whether a drug be covered by insurance plans. The panelists agree that this is likely to change.

Pressure to reduce prices, the soaring costs of clinical trials, and the difficulty of coming up with safe and efficacious treatments for chronic diseases have taken their toll on the pharmaceutical industry. Nevertheless, those closest to the industry are confident that they'll find a way, or more likely, many ways to prevail.