More research money doesn't mean more new drugs

The amount of money spent by the pharmaceutical industry to research and develop medications has increased dramatically, but the number of novel treatments put forward for Food and Drug Administration approval has grown at a far slower rate. This circumstance is particularly true if the product is not related to one already on the market, according to a Government Accountability Office report published in November and distributed in December 2006.

Specifically, the report found that, from 1993 to 2004, R&D funding increased 147% while new drug applications went up 38%. The growth for new molecular entities was only 7%. These numbers lead some experts to express concern that business priorities and the regulatory environment are supporting development of drugs similar to what is already on the market at the expense of therapies that fill a more urgent need.

"Me-too drugs are safer bets. There's a blockbuster mentality that does divert resources from innovation," said David Korn, MD, senior vice president of biomedical and health sciences research at the Assn. of American Medical Colleges. He was a member of the expert panel convened by the National Academy of Sciences for this project.

This report is the latest of several in recent years from government agencies and medical societies finding that the process to develop novel therapies is stagnant. The AAMC issued findings in conjunction with the FDA in January 2005 and blamed several factors. For instance, easier drug targets have been dealt with and remaining ones are more complicated to tackle -- requiring more time and investment before payoff.

"There have been just mind-boggling advances in the depth and power of the science that we have about human health and disease. But for every really big breakthrough, there are 100 new questions that nobody had been able to anticipate," Dr. Korn said.

Many who monitor the industry, though, say these numbers are on the cusp of improvement. "Drug development is still a very vibrant and dynamic process, and there are a lot of promising compounds entering clinical trials," said Alan Goldhammer, PhD, associate vice president for scientific and regulatory affairs for the Pharmaceutical Research and Manufacturers of America.

Along the way, researchers will have to meet the challenge of getting a better handle on some of the complex issues that serve as building blocks to medical advances. For example, the GAO's expert panel pointed to an urgent need for better tools to measure emerging biomarkers that would improve the prediction of drug efficacy and make the drug development process more efficient.

Another report, this one issued this month by the Tufts Center for the Study of Drug Development in Boston, found that significant progress was being made in developing technology that reduced the chance that a drug would make it all the way to the final stages only to fail. This paper agreed that drug approvals were lagging behind the amount of money spent on development but also found that the number of new drugs entering clinical trials had increased by 52% since 1998.

"[Drug developers are] about to see their efforts pay off in terms of improved success rates and greater numbers of new medicinal products reaching the marketplace," said Kenneth I. Kaitin, PhD, the center's director.

Easing the translation

But experts also say several pressing issues need to be addressed to free up the flow of drugs to patients. The GAO panel called for an increase in the number of physician-scientists who can translate new discoveries from the science bench to usable medications. The lack of translational researchers has long been a matter of concern for numerous medical societies, including the American Medical Association.

"It's a serious problem, and it's likely to get worse," said Myron Genel, MD, the AMA representative to the Institute of Medicine's Clinical Research Roundtable. "The economic environment within our academic health centers is making physician-scientists an endangered species."

Experts also would like to see more sharing of data either from the pre-clinical studies or failed clinical trials that are often never made public. The hope is that this would make the process more efficient by reducing the chance that researchers would investigate questions that already are answered or repeat others' mistakes.

Many observers also point to the need for changes in patent laws. Under the current system, the duration for which a company has market exclusivity is undercut by the time between registration and FDA approval -- a period that becomes inherently longer if the drug is novel and needs more research. Experts complain that this reality makes creating "me-too" drugs far more economically feasible.

Perhaps the most controversial possibility in the GAO report is the suggestion that the FDA establish a form of conditional approval for medications treating conditions that have few if any treatment options. This nod would allow drugs to be used outside of the clinical trial setting after shorter and smaller trials than are currently required and may involve limitations on marketing and advertising. Postmarketing studies also would be required. This approach is already used in certain cases, and some experts support it, particularly if its use was limited.

"We need to distinguish breakthrough drugs from me-too drugs. If a company wants to bring a new statin to the market, I believe the bar should be very, very high," said Jeffrey Leiden, MD, PhD, a member of the GAO panel and a partner in the life sciences venture capital firm Clarus Ventures. "[But] if there's a disease with no treatment and a very high unmet need, I believe the regulatory path should get the drugs out much more quickly."

Many were skeptical that this approach would work or make much of an impact. Approval times have declined significantly over the years, and some do not believe that shortening them more will have the desired effect. Also, in light of the fact that several reports have found serious flaws in the FDA's current postmarketing safety monitoring system, some worry that drugs without clearly defined safety profiles could be on the market for years and harm many before being pulled.

"The fact that a drug is not approved is not necessarily a bad thing," said Bruce Psaty, MD, PhD, professor of medicine and epidemiology at the University of Washington in Seattle.