Nonprofits and the Valley of Death in Drug Discovery

8/19/10

The research and development (R&D) process that ultimately leads to effective drugs is exceedingly difficult, and often the public does not understand the drug discovery pipeline. In a typical model, drug companies will research tens of thousands to millions of compounds and spend in excess of a billion dollars over a 10- to 20-year period just to have one drug reach the market.

The National Institutes of Health has aptly called the process of translating basic research into a viable product the “Valley of Death.” All too many promising drug candidates fall into this valley as the necessary testing for the Food and Drug Administration (FDA) and the complexity of human biology culminate in one failure after another. In 1996, the FDA approved more than 50 drugs; in 2009, that number plummeted to 26.

The reality today is that big pharmaceutical companies continue to rely on older breakthrough drugs for profits, and they are all too often failing in the development of effective new drugs. Moreover, drug companies are cutting back on long-term R&D in an attempt to improve immediate profits and returns for investors.

The challenges are daunting for “big pharma” (and everyone else), whether the subject is discovery, clinical trials, or manufacturing. Additionally, the industry must deal with the skepticism of citizens in this country and abroad who increasingly believe that drugs are too expensive, pharmaceutical companies are making too much money and the drugs being developed are not having enough impact on pressing diseases ranging from cancer to Alzheimer’s.

While big pharma is clearly struggling, there is a way to address the industry’s challenges by focusing on the fundamental mission of pharmaceutical innovation—developing effective drugs that will have a real impact on human health and diseases. I believe that nonprofit organizations (NPOs) can play an increasingly important role in providing solutions to the hurdles of large pharmaceutical companies today, and these NPOs can help transform the way drugs are developed and brought to market.

At SRI International, where I work, we are trying to provide pragmatic solutions to advance the drug discovery process. SRI conducts basic research on disease mechanisms, discovers and advances its own drugs and those of clients and partners, and provides the expertise and resources necessary to complete the preclinical development steps required to foster development candidates. There are a number of successful nonprofit organizations like SRI throughout the world—places like RTI in North Carolina or the Southern Research Institute in Alabama, to name a couple.

In the volatile world of pharmaceutical acquisitions and the cycle of biotechnology start-ups and failures, nonprofits provide needed stability. SRI has been around for more than 60 years, and about half of the senior staff in our Biosciences Division have been at SRI for 20 or 30 years. This is characteristic of the majority of similar NPOs—our goal is to recruit and retain the brightest and best minds in science and focus on problems that are relevant and enduring. NPOs may be the last stable environment in the rapidly changing biotechnology space.

Perhaps most important, nonprofits are helping to broaden the scope of research on disease. The pressure to produce a highly profitable drug, whether it is Viagra or Lipitor, can lead pharmaceutical companies down narrow paths for drug discovery. Many NPOs are taking different paths by focusing on targets that have implications for global health. We believe that by understanding the fundamental process of a virus such as HIV or Ebola or H1N1, we can understand other viruses as well and contribute to the development of effective vaccines. We believe that focusing on tuberculosis or malaria can have implications for understanding virulent staph and fungal infections.

When we get mired in the economics or politics of the pharmaceutical industry, we can lose sight of some essential facts—the development of effective drugs saves lives. In 1910, the average life expectancy of an American was 50 years. In 2010, our average life expectancy is 80 years, and drug development over the last 100 years has had a major impact on our increased life expectancy and quality of life. Through ongoing partnerships between nonprofits, universities, government agencies and the for-profit sector, we can take on the complex but achievable challenge of developing new drugs that will have profound effects on global health both near and far.

Walter H. Moos is vice president of the SRI Biosciences Division, a unique group of more than 200 researchers performing basic research, drug discovery, and preclinical development, at SRI International in Menlo Park, CA. Follow @

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  • http://users.lmi.net/sonyarap/ sonya rapoport

    This is a daunting article!!

  • Jona Ark

    Curious, how many compounds from SRI have been FDA approved?

  • http://www.sri.com Walter Moos

    Nearly 20 SRI compounds have advanced to human clinical trials, and to date 4 have received FDA approval. SRI has also helped its clients and partners advance well over 100 drugs into clinical trials, dozens of which have ultimately received FDA approval.

  • http://www.DELbiopharma.com Daniel Levy

    This is an excellent post focused on an area of great importance – neglected diseases. Mainstream pharmaceutical organizations, being bound by responsibilities to investors, target disease areas where both large patient populations exist and where patient populations can afford to buy medications. In third world countries, diseases such as malaria, typhoid, cholera, chagas and others cause tremendous stress on populations living under impoverished conditions.

    Because the paragigms for drug discovery apply to the discovery and development of all diseases, much can be learned from efforts emerging from SRI, One World Health, RTI and other non-profit pharma companies. The overall benefits will be aparent in both the ability to effectively treat neglected diseases while applying data from successful programs to more mainstream commercial efforts.