Whose health revolution?
There is a vast difference between the number of new drugs developed between 1975 and 1999 for tropical diseases and tuberculosis, and those developed for cardiovascular disease, despite the fact that the disease burden for the two groups is nearly the same.
... such impressive statistics should not obscure the fact that the benefits of the "global health revolution" have not been distributed evenly. Millions continue to die each year of preventable and treatable diseases. Communicable diseases killed 14 million people worldwide in 1999, mostly in developing countries.2 One cause of this is the vacuum in research and development (R&D) for medicines to treat the diseases of the poor.
There is a strong link between poverty and health. People from low- and middle-income countries carry a disproportionate burden of disease, particularly with regard to communicable diseases. Those living in absolute poverty (on less than one dollar per day) are five times more likely to die before reaching the age of five, and two and a half times more likely to die between the ages of 15 and 59.3 Infectious and parasitic diseases account for 25% of the disease burden in low- and middle-income countries, compared to only 3% in high-income countries.4 According to the World Bank, eliminating communicable diseases would almost completely level the mortality gap between the richest 20% of the world population and the poorest 20%.5
What kinds of needs does the
pharmaceutical market cover?
A represents Global Diseases, such as cancer, cardiovascular diseases, mental illness and neurological disorders, which constitute the major focus of the R&D-based pharmaceutical industry. Although affecting developed and developing countries, most people in developing countries who have needs for drugs to treat these diseases cannot afford them, and are thus not covered by the pharmaceutical market.
B represents Neglected Diseases,
such as malaria and tuberculosis (TB), for which the R&D-based pharmaceutical industry has only marginal interest. Although also affecting people in wealthy countries, for example TB patients or people who get malaria while travelling, these illnesses primarily affect people in developing countries.
C represents the Most Neglected Diseases, such as sleeping sickness, Chagas disease and leishmaniasis, which exclusively affect people in developing countries. Because most of these patients are too poor to pay for any kind of treatment, they represent virtually no market and for the most part fall outside the scope of the drug industry's R&D efforts, and thus outside the pharmaceutical market.
Z represents the part of the pharmaceutical market for products addressing conditions other than those which are purely medical (such as cellulite, baldness, wrinkles, dieting, stress and jet-lag), which nonetheless represent a highly profitable market segment in wealthy countries.
The vacuum in drug R&D for the diseases of the poor
Eliminating the mortality gap will likely remain an elusive goal, because R&D efforts are not addressing many of the communicable diseases that plague developing countries. An analysis of drug development outcomes over the past 25 years shows that only 15 new drugs were indicated for tropical diseases (11 2) and tuberculosis (2).6 These diseases primarily affect poor populations and account for 12% of the global disease burden. In comparison, 179 new drugs were developed for cardiovascular diseases, which represent 11% of the global disease burden (Figure 1A).
Too little money is going into health research that addresses the needs of the world's poorest people. While it might be expected that health research would concentrate on the areas where the needs are greatest, the reality is quite different.
Only 10% of global health research is devoted to conditions that account for 90% of the global disease burden - an imbalance that has been referred to as the 10/90 disequilibrium.7
Heavy reliance on an increasingly consolidated and highly competitive multinational drug industry to generate new medicines has left the development of lifesaving drugs subject to the forces of a market economy. Currently, it is largely purchasing power that is defining research agendas and priorities, which means that poor people's health needs are not being met.
This failure does not rest exclusively on the shoulders of the private sector. Governments hold the ultimate responsibility for ensuring that peoples' basic health needs are met. They have the responsibility to take appropriate action when market forces fail to address these needs. In the past few decades, despite clear evidence of waning private sector interest in the diseases of the poor, government action has been inadequate.
While it is urgent for decision-makers to address this issue, efforts are hampered by a lack of comprehensive information and understanding on the dynamics of R&D into diseases that primarily affect poor people. This lack of information makes it more difficult for policymakers to understand the extent of the problem and make informed decisions to address the crisis.
What are neglected diseases? A seriously disabling or life-threatening disease can be considered neglected when treatment options are inadequate or don't exist, and when their drug-market potential is insufficient to readily attract a private sector response. Government response is also inadequate. In short, for
neglected diseases, there has been a failure of the market and a failure of public policy. Neglected diseases mainly affect people in developing countries. Public research institutes in the industrialized world do not view these diseases as either a priority or a major threat to their populations, and research-based drug companies do not pursue promising compounds for drugs to treat these illnesses because of an inadequate return on investment.
A look at the dynamics of this market failure shows that a distinction between "neglected" and "most neglected" diseases can also be made. For the "most neglected" diseases, patients are so poor that they have virtually no purchasing power, and no amount of tinkering with market forces is likely to stimulate interest among drug companies. If the market is failing poor people suffering from neglected diseases, it has failed people suffering from the most neglected diseases even more (Figure 1B). Some examples of neglected diseases are malaria, tuberculosis, human African trypanosomiasis (sleeping sickness), South American trypanosomiasis (Chagas disease), Buruli ulcer, dengue fever, leishmaniasis, leprosy, lymphatic filariasis and schistosomiasis. All but the first two can be considered most neglected diseases.
Tropical diseases are good examples of neglected diseases. Of the 1,393 total new drugs approved between 1975 and 1999, only 1% (13 drugs) were specifically indicated for a tropical disease.8
Number of companies (out of 11 respondents) with research and development activities targeting drugs for neglected diseases
|Disease||R&D Spending||Screening||Pre-clinical or Clinical Development||Product to market in last five years|
(includes viral, bacterial and fungal diseases)
Fig.1C: Methodology: The survey was sent to the CEOs and/or Directors of Research of 20 pharmaceutical companies in Europe, Japan, and the US. The questionnaire inquired about overall resources devoted to infectious diseases, and specific resources devoted to particular neglected diseases. The survey stated that individual company names would not be disclosed when reporting the results. Results relied on self-reporting and reports were not independently validated.
An empty pipeline An examination of current research efforts in the pharmaceutical industry reveals that the pipeline of drugs for neglected diseases is virtually empty (see Figure 1C). In spring 2001, the DND Working Group and the Harvard School of Public Health sent written questionnaires to the world's top 20 pharmaceutical companies to assess the level of R&D activity in several neglected diseases (sleeping sickness, leishmaniasis, Chagas disease, malaria and tuberculosis).9 Thirteen companies responded, eleven of which completed the questionnaire. Of the two others, one indicated no reportable research activities in infectious disease and the other said time constraints prevented completion of the survey. The eleven companies who responded fully include at least six of the top ten. Together the respondents represent nearly US$117 billion of the global pharmaceutical market, which is estimated at $406 billion for 2002.10
Overall R&D budgets for the responding companies ranged from $500 million to greater than $1 billion per year. Of these amounts, 25% or less was devoted to R&D for infectious
diseases. Eight out of the eleven companies spent nothing at all over the last fiscal year on R&D for the most neglected diseases included in the survey (sleeping sickness, leishmaniaisis and Chagas disease); one company did not answer this question. Only two companies reported spending on malaria. Five companies reported spending on tuberculosis, one of which devoted over 15% of its infectious disease R&D budget to tuberculosis and malaria. However, seven companies reported spending less than 1% on any of the five diseases included in the survey or failed to respond to that question. All other infectious disease spending fell under the category "other," which includes viral, bacterial and fungal diseases.
Company involvement in various stages of the R&D process was also very limited (see Figure 1C). None of the companies screened chemical compounds for usefulness against sleeping sickness, Chagas disease or leishmaniasis, one screened for malaria, and four screened for tuberculosis. Similarly, no company had any compounds in clinical development for sleeping sickness, while one company reported having at least one compound in pre-clinical or clinical development for Chagas disease and one company reported the same for leishmaniasis. There seemed to be slightly more activity for malaria and tuberculosis: a few companies have products in pre-clinical or clinical development or have brought a product to market within the last five years.
Yet, despite low in-house investment into neglected diseases, participation in public-private partnerships was considerable. Six of the eleven companies reported participation in these kinds of partnerships, with individual financial commitments ranging from $500,000 to $4 million.
While the survey demonstrated some activity in neglected diseases - above all in tuberculosis - by and large, it indicated that private sector investment into this field was minimal.
An equally bleak picture emerges from recent surveys on new medicines in development conducted by the US drug industry lobby group, the Pharmaceutical Research and Manufacturers of America (PhRMA).11 Of the 137 medicines for infectious diseases in the pipeline during 2000, only one mentioned sleeping sickness as an indication, and only one mentioned malaria. There were no new medicines in the pipeline for tuberculosis or leishmaniasis. PhRMA's current "New Medicines in Development" list shows eight drugs in development for impotence and erectile dysfunction, seven for obesity, and four for sleep disorders.12
1) World Health Organization, Health: A precious asset, Accelerating follow-up to the World Summit for Social Development, proposal by the World Health Organization, WHO/HSD/HID/00.1 (Geneva: World Health Organization, May 2000).
2) World Health Organization, The World Health Report 2000, estimates for 1999, Mortality by sex, cause and WHO Regions. (Geneva: World Health Organization, 2000).
3) World Health Organization, Health: A precious asset, Accelerating follow-up to the World Summit for Social Development.
4) World Health Organization, The World Health Report 1999, estimates for 1998, Burden of disease by cause, sex and mortality stratum in WHO Regions. (Geneva: World Health Organization, 2000). Disease burdens are expressed in DALYs, or Disability-Adjusted Life Years.
5) Davidson R. Gwatkin and Michel Guillot, "The Burden of Disease among the Global Poor: Current Situation, Future Trends and Implications for Strategy" (Washington, D.C.: World Bank, 2000).
6) Patrice Trouiller et al., "Neglected diseases and pharmaceuticals: between deficient market and public health failure," forthcoming publication, 2001. Note: Disease burden is expressed in DALYs, or Disability-Adjusted Life Years. Tropical diseases include parasitic diseases (malaria, African trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, onchocerciasis), dengue, diarrhoeal diseases, intestinal nematode infections, leprosy and trachoma. For these diseases, the following 11 new chemical entities were developed between 1975 and 1999: halofantrine, mefloquine, artemether, atovaquone (malaria); benznidazole, nifurtimox (Chagas disease); albendazole (helminth infections); eflornithine (African trypanosomiasis); ivermectine (onchocerciasis); oxamniquine, praziquantel (schistosomiasis). In addition, two reformulations of already existing drugs came onto the market: pentamidine isetionate (African trypanosomiasis) and liposomal amphotericin B (leishmaniasis). The two new drugs for tuberculosis are pyrazinamide and rifapentine.
7) Global Forum for Health Research, The 10/90 Report on Health Research. [Online]. (2000). Available: http://www.globalforumhealth.org.
8) Patrice Trouiller et al., "Neglected diseases and pharmaceuticals: between deficient market and public health failure," forthcoming publication, 2001.
9) Dyann F. Wirth, survey for the Drugs for Neglected Diseases Working Group, Switzerland, May 2001. [Online]. Original survey and letter available: www.accessmed-msf.org.
Andra Brichacek, Top 50 Phamaceutical Companies of 2000, Pharmaceutical Executive, April 2001.
Available: www.pharmaportal.com/articles/pe/pe0401_062-82.pdf [2001, August 6].
10) Six respondents were among the top ten companies worldwide, by sales; two other respondents chose to remain anonymous.
11) Pharmaceutical Research and Manufacturers of America. New Medicines in Development for Infectious Diseases: A 2000 Survey. [Online].
Available: http://www.phrma.org/searchcures/newmeds [2001, August 22].
12) Pharmaceutical Research and Manufacturers of America. New Medicines in Development. [Online]. Available: www.phrma.org [2001, August 22].