Healthy Skepticism Library item: 8587

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Publication type: news

Goozner M.
The Future of Non-Profit Drug Development
GoozNews 2007 Feb 9
http://web.archive.org/web/20080829173522/http://www.gooznews.com/archives/000618.html#more

Full text:

This is a summary of a talk I will be giving to the Association of European Hospital Pharmacists in March.

The United States is the world leader in investing in biomedical research and development. In the public sector, the National Institutes of Health spent $28.6 billion in 2005, largely for basic science research. The pharmaceutical industry spent an estimated $39 billion in 2004. This includes investment in the U.S. by U.S.-based firms, investment overseas by U.S. firms, and foreign companies’ R&D expenditures in the U.S. Indeed, over the past quarter century, the private sector’s investment in the search for new medicines has grown eight percent per year on average, faster than the industry’s growth in sales and profits.

Despite this massive public and private effort, output, as measured by the number of new drugs, biologics, vaccines and devices approved for use by regulatory bodies like the U.S. Food and Drug Administration, has slowed in recent years. Last year, the FDA approved just 21 new drugs and biologics, the second lowest total since 1993. Moreover, about half of these new drugs were not given priority status by the FDA, which meant they were not considered a significant new advance in medicine. This significance ratio has held steady for over a decade. Clearly, the steady increase in private and public R&D spending is generating diminishing returns, whether measured by return on investment or public health.

This falloff in R&D productivity has occurred despite extraordinary advances in the technology of drug discovery. The public sector’s massive investment in basic science, mostly conducted at universities, has uncovered the complex details of how cells work and the chemical interactions of their constituent parts. A government-led project decoded the human genome; scientists are rapidly identifying the functions of the proteins that the genome produces; and, for over 30 years, we have had the bioengineering skills to reproduce those proteins and monoclonal antibodies in mass quantities. We can use these tools to identify the biochemical interactions of many diseases. This in turn has given scientists hundreds of potential targets for drug therapy.

To go after those targets, scientists have developed new tools like mass screening and sophisticated bioassays affixed to computer chips to identify potentially effective new drugs. Advances in biochemistry and x-ray crystallography have given medicinal chemists the ability to design and synthesize new drugs capable of affecting those targets faster and more accurately than ever before. Finally, the drug industry and government have financed and built an infrastructure for conducting clinical trials that far surpasses what existed in previous eras.

So why is output slowing down? I would offer two simple hypotheses for the decline in R&D productivity. First, the scientific drug revolution pioneered by Europeans like Paul Erhlich and Gerhard Domagk has evolved to the point where it is now a mature industry. In the past century, scientists have developed drugs for most of mankind’s common maladies. We can kill most of the microbes that invade our bodies. We can control blood pressure, allergies, minor aches and pains, and acid indigestion. We can cure a few cancers and prolong life for a few more. We can give drugs to prevent some heart attacks. We have even engineered a few proteins like recombinant human erythropoietin or granulocyte-colony stimulating factor that are remarkably effective because they replace factors that, when certain diseases strike, are no longer produced in sufficient quantities by the body. And, for many of these disease states, we are now on the second or third generation of drugs.

In other words, the low-hanging fruit of medicinal chemistry has been picked. To be an innovator today, you must discover cures for chronic diseases like diabetes, most cancers, dementia (Alzheimer’s disease), rheumatoid arthritis, and the other maladies of aging societies. Will there ever be a pill to slow the aging process, or the diseases that accompany aging? That is going to require a lot more investment in basic research to understand the chemical cascades that affect many of us as we age, and then a lot more research beyond that to understand how we can safely intervene in the process. I wouldn’t count on rapid success.

The second reason for declining productivity is that industry R&D largely ignores areas where it is possible to have a tremendous impact very quickly and where there is tremendous need: the neglected diseases of the developing world. Industry does not seek the cures for drug resistant tuberculosis, malaria, leishmaniasis, Chagas disease or hookworm. It could spend its vast resources developing drugs and vaccines for these conditions, but it doesn’t because there is no market. It’s not that there aren’t billions of potential customers for these treatments. It’s that those potential customers have very little money. And when there is no discretionary income for medicine, there is no drug market. This is a classic case of what economists call market failure.

But rather than look for ways to artificially stimulate demand in these needy countries (by lobbying for greater aid, for instance), the drug industry instead devotes a substantial share of its R&D budgets to developing new drugs in their existing market that are nothing more than replacements for older drugs that are losing patent protection. Upon occasion, they are superior to the older drugs. But even when they are, it is usually not by much. This strategy may be good for their bottom lines, but it provides a very small return for public health.

In the years ahead, the greatest advances in biomedicine will come from two arenas: greater investment in the basic science behind the chronic diseases of aging; and concerted campaigns to develop drugs and treat the infectious diseases that are ravaging the two-thirds of the globe inhabited by poor people. Since the private sector is poorly placed to tackle either problem, it will be the public and non-profit sectors that will have to play the leading role.

To leap ahead in our efforts to come up with therapeutics for chronic diseases of aging, governments will need to increase their investment in basic science. Let’s take one example: the fight for a cure for Alzheimer’s disease (AD). Great Britain’s National Institute for Health and Clinical Excellence is under pressure from the two companies that make cholinesterase inhibitors, including donepezil or Aricept, to make them available for the early stages of the disease. Yet the Cochrane Collaboration last year said that “there is little evidence that donepezil improved cognitive function, and no evidence that donepezil delays progression to AD.” Does this mean that the years of basic and applied research that went into developing the cholinesterase inhibitors was wasted? No. It only means that the mechanism that they inhibit does not by itself halt the progression of the disease.

To make progress against AD and other degenerative diseases of aging, our governments need to step up targeted research. We must learn so much about the natural history of this disease that drug developers not only have targets, but have validated targets. This strategy has a proven track record. The targeted research campaign that developed the drugs that can now control HIV/AIDS was initiated and largely funded by the U.S. government. Governments also need to rethink the global intellectual property regime, which maximizes commercialization but in its present form may be inhibiting the scientific collaboration crucial to innovation by building walls of secrecy between researchers.

In the neglected diseases arena, non-profit drug developers like Medicines for Malaria Venture, based in Geneva, One World Health, based in San Francisco, and the Global Alliance for TB Drug Development, based in New York, are blazing the trail to the future. Funded largely by the Bill and Melinda Gates Foundation and other charitable foundations, these organizations are not only developing drugs, but are reaching intellectual property agreements that ensure that their products will be affordable in the developing world if and when they are developed. Since the private sector’s profit imperative prevents it from tackling the world’s most pressing public health problems, this emerging non-profit sector will have to step into the breach. And I’m sure it will. Because as we’ve seen so many times before in medical history, it is human needs and the tireless efforts of committed scientists that drive pharmaceutical innovation, not private profit.