HOUSTON. The World Health Organization (WHO) estimates that less than 10% of the $56 billion spent worldwide each year on health research is directed toward diseases that afflict 90% of the world's population. According to U.S. Senator John Kerry, "Market disincentives, especially the lack of a viable, cash-rich market, play against investment into these vaccines." In addition, many drugs effective against tropical diseases are no longer available or in danger of being pulled from the market because they are unprofitable, say researchers from the Baylor College of Medicine and Centers for Disease Control and Prevention (CDC). "Parasites are a very common causes of disease in the world but because there is no market for antiparasitic drugs, drug companies are discontinuing production," says Clinton White of the Baylor College of Medicine in Houston. This is because parasitic diseases are most commonly found in developing countries without funds to effectively support production of these drugs.
Many drugs used to treat tropical diseases are only occasionally used in developed countries making domestic production prohibitively expensive. Piers Whitehead of Mercer Consulting notes that, due to the high cost of new drug development, large drug companies are reluctant to develop drugs unless the estimated market is more than $350 million in annual sales. 1,223 new drug compounds were commercialised between 1975 and 1997. However, Patrice Trouiller, a consultant with Medecins sans Frontieres (MSF or Doctors Without Borders) observes that only eleven were designed for tropical diseases.
Dr. White and colleague Anne Moore from the Centers for Disease Control (CDC) began studying this phenomenon last summer when some clinicians noticed it was difficult to acquire the drug praziquantel. Praziquantel is used to treat schistosomiasis, a parasitic disease that can cause chronic liver damage and affects about 200 million people worldwide. The drug's manufacturer had stopped producing it in the United States because it was losing money. "Here we had a perfectly treatable infection and no access to a drug to treat it in this country," says White. "We have to recognise that parasitic diseases are a real public health problem, but that the market for financially sustainable drugs just isn't there."
While the maker of praziquantel has since agreed to resume production, White and Moore have found numerous similar instances where effective drugs are no longer being made available in the United States, and sometimes worldwide, because they are not profitable. One example is bithionol, which hasn't been manufactured since 1979. Bithionol is used to treat infection with Fasciola hepatica (liver fluke), a parasite that can cause severe liver damage. The CDC stocks and distributes the only U.S. supply of this drug.
Robert Ridley and Winston Gutteridge of the Medicines for Malaria Venture (MMV) observe, "The problem of ensuring the development and commercialisation of new drugs for indications where the market is weak has to be addressed both through:
• the 'pull' of enhancing market attractiveness to pharmaceutical companies so that they engage in product commercialisation.
• the 'push' of providing R&D support to obtain drug candidates of high quality that are capable of taking their place in the market. This reduces the risk to companies engaging in early R&D and reduces their costs, including their opportunity costs, enabling them to engage in product commercialisation for a smaller commercial return."
MSF favours an approach falling into the second category — making a virtue of the rarity of tropical diseases in developed countries. Since 1983, the U.S. has offered incentives in the form of tax credits and marketing monopolies to companies willing to develop drugs for "orphan" diseases, which afflict fewer than 200,000 people and offer markets too small to attract major pharmaceutical companies. The European Commission is preparing similar legislation and Dr. Trouiller of MSF is lobbying for tropical diseases to be included in it.
The Lifesaving Vaccine Technology Act of 1999, introduced by Representative Nancy Pelosi and Senator Kerry in the U.S. Congress, aims to encourage development of vaccines for malaria, tuberculosis and HIV, which together kill almost 8 million people annually. Providing 30% tax credits on R&D expenses, the legislation would cost about $25 million annually.
Development of an alternative to bithionol, triclabendazole, provides an example of collaboration between WHO and the private sector to develop and assess the efficacy of tools for the control of communicable diseases. Working in conjunction with WHO and Novartis Pharma, the Egyptian Ministry of Health has registered triclabendazole for human use and its registration for human use is currently under way in other endemic countries.
Walter Vandersmissen, head of government affairs at SmithKline Beecham Biologicals, believes the best way to stimulate new development is to prove that sustainable markets can be created for candidates already on the shelf. MMV is taking this approach bringing together public-sector organisations and drug companies under WHO auspices. MMV hopes to register one new anti-malarial product every five years. To do so, MMV is likely to need $30 million annually from public funds and philanthropic institutions.
Parasitic infections are commonly found in pets and the pharmaceutical industry has found this to be a profitable market that may offer human drug candidates. For example, ivermectin (Mectizan), a Merck drug commonly used to treat heartworms in dogs is also effective against a number of parasitic diseases including onchocerciasis (river blindness). Merck has found ivermectin veterinary use so profitable that the company has been giving the drug away free in developing countries. Eric Ottesen, of WHO's Center for Tropical Diseases, and one of the world's leading authorities on lymphatic filariasis, says that Merck's donation of ivermectin "has transformed the ways in which we now think of approaching some of the most intractable problems of public health in the developing world. The expansion of the ivermectin donation program to include lymphatic filariasis in Africa, which promises to help millions of people in some of the poorest areas of Africa, provides an outstanding example for others to follow."
Modern life styles could be fostering the spread of parasitic and other largely tropical diseases into the developed world. For example, "More and more the population is travelling to areas where parasitic diseases are endemic. If you have an infection you got overseas, you're going to need these drugs to treat it here in the United States," says White. Could this lead to increased availability of medicines for tropical diseases?