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Drugs for all

Drug companies largely ignore poor countries, report Ohad Oren and Norberto Krivoy

In many poor countries economic and social factors combine to prevent patients’ access to essential drugs. And attempts to lessen the crisis have largely not helped. In May the World Health Organization developed a set of strategies to combat the problem. They focus on improving research and development for drugs for diseases that have been underfunded and to improve access to existing drugs. WHO hopes that this will encourage “innovation plus access” for diseases prevalent in the developing world, two ideas that have often been seen to work against each other.¹ The WHO assembly has agreed to penalise anticompetitive practices surrounding drug patents (box) and to attract research and development by giving financial incentives.¹ WHO wants all member states to contribute to the development of new drugs, scaled according to their country’s wealth. Margaret Chan, WHO’s director general, praised the initiative as “a major breakthrough for public health that will benefit many millions of people for many years to come.”²

Challenges for drug companies

Drug companies face many obstacles in the development and manufacture of a drug. The research and development process is lengthy and costly. Typical spending for a single successful drug is $800m (£460m; €600m).^{3 4} For every drug that reaches the market about 7000 compounds are tested in preclinical trials, and only five get tested in full scale human clinical trials.⁵ Drug companies must find ways to balance the costs of research into drugs that fail: today’s profits have to pay for tomorrow’s research.

The development of drugs has become more costly because companies must minimise therapeutic risks using more expensive laboratory, clinical, and manufacturing practices.³ They must incorporate more and more patients into studies of increasing length so that rare or unexpected adverse events are more likely to be seen.⁶

Development in poor countries

Research and development for diseases that are prevalent in poor countries incurs additional problems. Developing countries’ spending for health services is low. In 2001 it was just over $23 per capita.⁷ For diseases such as malaria—99% of cases are in poor countries—the incentive to invest in research and development is low.⁸ Drugs for other diseases that are common in the developing world are similarly unprofitable, including schistosomiasis, Chagas disease, and ascariasis.⁸

Generics—good and bad

Before 1984 generic drugs, which are discounted, chemically identical versions of original protected drugs, were considered uneconomical to produce. The makers of generic drugs have to conduct the same tests of safety and efficacy that are required of the makers of original branded drugs. The Hatch-Waxman Act injected price competition into the drug market by shortening the approval process for generic drugs, reducing the need for clinical trials, and allowing companies to apply for approval before the patent for the original protected drug expired.⁹ Consequently, the production of generic drugs has become less financially risky.

The largest Indian generic drug company, Cipla, sells generic drugs for HIV at a fraction of their original price. Yusuf Hamied, chairman, said, “There is an epidemic on our hands. How can you justify selling something that costs $200 for $10 000?”¹⁰ Drug companies should not derive excessive profits, he argues, letting treatable illnesses extinguish millions of lives in the developing world.

The industry has flourished: generics now comprise 63% of all US prescriptions for drugs.⁹ Generic drugs are also responsible for attenuating the overall price rises for prescription drugs. For the manufacturers of branded drugs, which hold the patents, this creates a problem. By the time the patent expires it is less likely that the company has regained the revenue it needs to channel back into research and development.

Partnerships

Drug companies have focused on the most profitable parts of the market—drugs for cardiovascular diseases, cancer, dermatological disorders, and infectious diseases. Tropical diseases have largely been ignored because of market forces (table).^{4 11} Of 1556 new chemical entities marketed from 1975 to 2004 only 10 were indicated for the most neglected tropical diseases.¹¹ To highlight the absurd, in the 1983-7 period alone 16 new antibacterial agents were approved for clinical use.¹²

Disease	No drugs developed, 1975-2004	Global prevalence (millions)
Malaria	8	247
Chagas disease	2	16-18
African trypanosomyasis	2	0.6
Leishmaniasis	2	12
Onchocerciasis	1	37
Schistosomiasis	2	207

In the late 1980s, however, the drug company Merck created a partnership to control a neglected tropical disease, namely onchocerciasis.¹⁶ Merck collaborated with the onchocerciasis control programme sponsored by the United Nations. The partnership has provided 300 million treatments of ivermectin, and further joint programmes for the elimination of onchocerciasis were created. The drug company Pfizer has taken similar steps by donating the antibiotic azithromycin, used to treat trachoma, to the international trachoma initiative, a non-profit making organisation based in the United States. Trachoma is the most common cause of preventable blindness.¹⁶ Other collaborative efforts between WHO, Merck, and GlaxoSmithKline have resulted in the near elimination of lymphatic filariasis in Egypt, Samoa, and Zanzibar, and of trachoma in Morocco.¹⁶ But such interventions won’t lead to extinction of neglected diseases. The United Nations’ millennium development goal is to halt and begin to reverse the spread of neglected tropical diseases by the year 2015. This will require coordinating the activities of different partnerships¹⁷ because there is extensive geographical overlap and endemicity among various tropical diseases.¹⁸

What next?

Donation of drugs by industry has reduced disease burden in some countries. Such interventions are insufficient though. Our main goal should be to increase the negligible research and development of drugs for neglected diseases.

Competing interests: None declared.

Provenance and peer review: Not commissioned; externally peer reviewed.

See “Access to essential drugs” (Student BMJ 2002;15:282-3, http://student.bmj.com/issues/07/07/life/282.php) and “Neglected tropical diseases” (BMJ 2007;335:269-70, doi:10.1136/bmj.39281.645035.80).

Ohad Oren fourth year medical student Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
ohadoren@gmail.com
Norberto Krivoy director clinical, pharmacology instituteclinical associate professor
Student BMJ 2008;16:392 | 10

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