EVENTS

Date:	Tuesday, February 7, 2006
Time:	2:00 PM -- 4:00 PM
Location:	Wohlstetter Conference Center, Twelfth Floor, AEI 1150 Seventeenth Street, N.W., Washington, D.C. 20036

February 2006

Getting the Most Innovative Drugs to Market: What Can the FDA Do?

Drugs developed by the pharmaceutical research industry have revolutionized health care. Yet, in recent years there has been a decline in the number of innovative new drugs reaching the market, despite extraordinary advances in the basic and applied science upon which these new developments depend. At a February 7 AEI conference, panelists discussed the most potent forces in drug development, including the Food and Drug Administration (FDA), the government agency at the very center of pharmaceutical drug development. The FDA exercises nearly unlimited power over drug research--from the earliest clinical trials to final product approval--and its scientific expertise and regulatory philosophy can determine whether and when dramatic research breakthroughs are translated into cures. But can the agency keep up with new scientific innovations?

Scott Gottlieb
Food and Drug Administration

Contrary to popular belief, speed and safety in drug development are not opposing virtues. In fact, quite the opposite is true. New and innovative scientific technologies and regulatory approaches can make the drug development process not only faster, but safer and more precise. The past is full of examples where the use of novel diagnostic tests and biomarkers has both accelerated the development of therapies and enabled drug developers and the FDA to glean more accurate safety and efficacy information. Today the FDA is evaluating a number of new scientific tools including surrogate markers for identifying toxic effects in vital organs that could help weed out unsafe drugs before market approval and even before the onset of clinical trials.

By and large, the many years spent taking a drug from discovery to bedside reflect a long and cumbersome developmental pathway, rather than a lengthy FDA review process.
However, the FDA still has a direct impact on the nature and extent of the drug testing process by setting the requirements that companies must meet in order to gain regulatory approval. In too many cases, tools that were literally developed decades ago--in some cases, fifty years or more--are being used to assess the efficacy of medicinal candidates. The FDA is committed to looking internally at ways to modernize its own evaluation methods and in turn the methods it allows drug companies to use to demonstrate safety and effectiveness.

Over the past couple decades, spectacular advances in genomics and proteomics have enabled scientists and physicians to conclude or at least theorize how medicines halt disease progression and other medical ailments. Yet, in the same time frame, the drug evaluation process and thus the practice of medicine has remained empirical in nature. A more mechanistic approach to drug development that incorporates biomarkers and diagnostic tests will allow physicians to predict which patients will respond to particular therapies and to what extent.

As a nexus for the majority of drug developers, the FDA has a unique vantage point that can be used to identify obstacles to a quicker and more informative developmental process. By spearheading public and private partnerships, the FDA is working to hasten patient access to potentially lifesaving treatments while maintaining high standards of safety.

Sid Gilman
University of Michigan

Alzheimer’s disease is a slow and devastating condition that impairs the parts of the brain that control thought, memory, and language. Fifty percent of people over the age of eighty-five suffer from Alzheimer’s or some other form of dementia. According to conservative estimates, Alzheimer’s disease currently affects 4.5 million Americans with 470,000 of these cases appearing in 2005 alone. Medicare spent $91 billion treating the symptoms of Alzheimer’s in 2005 and expects to spend $160 billion by 2010. Yet little has been done by the medical and scientific community to develop ways to treat the source of Alzheimer’s disease.

Alzheimer’s is characterized by the presence of two abnormal structures: beta-amyloid plaques and neurofibrillary tangles. Dale Schenk and his colleagues immunized mice with a material that fostered the development of beta-amyloid antibodies. The treatment successfully eliminated existing deposits of the beta-amyloid plaques and prevented the formation of new plaques. The immunization appeared to be safe in a Phase I trial and caused a marked improvement in patient performance on a cognitive function test. Unfortunately, in Phase II trials, an inflammatory reaction developed in 6 percent of participants, and the trial was halted following the fourth event.

Nonetheless, the study provides the medical community with a “proof of concept principle” that could pave the way for potentially lifesaving immunotherapies. However, the FDA has been reluctant to lower regulatory hurdles that could bring these promising therapies to market sooner. While the advisory and review process at the FDA works well, it takes too long to approve drugs especially in light of the urgency with which these drugs are needed by the elderly. The developmental process can take seven to ten years from the time the molecule is available and tested on animals to the time it becomes available for FDA approval.

The FDA is too timorous when it comes to side effects associated with therapeutics for Alzheimer’s disease. With the baby boomers getting older, Alzheimer’s is growing to epidemic proportions, which raises serious health and economic concerns. Delaying the onset of Alzheimer’s by five years would decrease the prevalence of the disease by 50 percent. Regrettably, without more regulatory flexibility in drug evaluation and approval, the FDA is incapable of bringing new and innovative drugs to the market in a timely fashion.

New scientific approaches along with increased technological capabilities may make it possible to recognize and track the progression of a disease with greater precision and accuracy. These same technologies could be used to reduce the size and length of clinical trials. Regardless of the way in which drugs are determined to be safe and effective, one thing is certain: the FDA must find a way to get beneficial new treatments to the people who need them most before it is too late.

John Orloff
Novartis

Unprecedented challenges facing the pharmaceutical industry have spurred a collaborative process to advance drug development more quickly. A number of opportunities exist where industry and regulatory authorities can work together to hasten patient access to innovative medicines. These include establishing an inventory of biomarkers that could serve as surrogate endpoints in clinical trials and developing diagnostics that could identify patients who would most likely respond to medical interventions.

Health authorities need to embrace industry-generated simulations and take into account causal- and model-based evidence, together with clinical results, when making regulatory decisions. If a new medicine presents a significant advance over existing therapies in a disease area, the FDA should accelerate its entry onto the market through the use of biomarkers or other proxies of clinical outcomes. Fast-track approval through the subpart H mechanism needs to be extended beyond the realm of oncology drugs.

An expanded partnership between regulatory authorities and the drug industry is imperative to transforming drug development and improving public health. Enhancing data exchange and incorporating models and simulations into decision making will compress testing and evaluation timelines and ultimately speed the delivery of novel medicines to patients with unmet needs.

John E. Calfee
AEI

There is nothing on the face of the earth quite like FDA regulation. It is extremely comprehensive, encompassing almost every stage of pharmaceutical and biotechnology drug development. It begins in the earliest phase of clinical trials and continues on from market approval all the way through manufacturing, marketing activities, and post-marketing research. By contrast, in the airplane and automobile industries, where product development is complex and safety is paramount, regulatory scrutiny is nowhere near as exhaustive and barely touches research and development or manufacturing.

FDA regulation is also extraordinarily opaque. It is truly difficult for the rest of the world to discern what actually goes on between industry and the FDA. Naturally, a system that is so extensive, so largely hidden from view, and so critical to public health lends itself to intense concern and criticism from outside parties. One such criticism that has saturated the editorial pages of medical journals and newspapers alike is that the FDA staff has gotten too close to the industry, and that their cozy relationship has compromised safety.

Ever since the Vioxx withdrawal, critics have been accusing the FDA of becoming increasingly biased toward too little safety and too much freedom for firms to introduce drugs and keep them on the market when safety concerns arise. In truth, no such situation has occurred. If anything, the FDA staff faces strong incentives to err on the side of excess caution rather than hasty innovation.
 
AEI research assistant Elizabeth DuPre and AEI intern James Placa prepared this summary.