Over the past decade, the pharmaceutical industry has been steadily increasing its investment in lifestyle drugs (see next page). Although this effort is geared more toward capturing revenue from the developed countries of the West, there can occasionally be a positive outcome for developing nations. Eflornithine is one such example and its development also illustrates just how far public-private partnerships have come.
Eflornithine is used to treat advanced human African trypanosomiasis (HAT), or sleeping sickness, the incidence of which has increased nearly a 100-fold in the last 40 years, returning to levels similar to those in the 1950s. But the compound originated from a depilatory product marketed to women in North America by Bristol Myers Squibb (BMS). So how did a cosmetic product recently become a life-saving drug for a parasitic disease?
Originally developed in the 1970s as an anti-cancer molecule called difluoro-methyl-ornithine (DFMO), the agent failed in trials, but had the same hair loss side effect associated with other chemotherapy drugs. During this period, Cyrus Bacchi, from Pace University, New York, noticed that DFMO showed marked anti-trypanosome activity in animals, and in 1983, Belgian physician Henri Taelman used the renamed eflornithine to treat a comatose woman in Antwerp. She began to revive within a day, earning eflornithine the soubriquet "the resurrection drug."
However, set against the backdrop of war, economic deterioration and collapse of rural health infrastructure in countries such as Angola, Congo and Sudan, the potential of eflornithine to mitigate HAT suffering languished. This, combined with eflornithine's difficult administration procedure—it requires two-week hospitalization and continuous IV infusions, requirements difficult to satisfy in HAT-endemic regions—means that the compound had no real revenue value for pharmaceutical companies. In 1995, Aventis halted its production, along with that of two other drugs for HAT. Simultaneously, Bayer AG threatened to stop making a fourth anti-HAT drug, suramin, leaving a growing number of patients in Africa bereft of treatment for their disease after the three-year stock ran out.
Anticipating the calamity, health agencies such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention, and non-governmental organizations
Médecins Sans Frontières (MSF) and Epicentre, began looking for a way to persuade pharmaceutical companies not only to resume production, but to provide the drugs free or below cost. Jean Jannin of WHO's Department of Communicable Disease Surveillance and Response in Geneva, was instrumental in the lobbying effort. "We established a special network to try to find a solution. The first step was to have Aventis give WHO a license and transfer the technology to produce the drug."
But there were two problems: WHO and MSF are not drug manufacturers, and because eflornithine is difficult and expensive to make, alternate producers were not easy to find. Second, availability of drug in itself was not enough. Equally important were surveillance and screening, training of health workers and rehabilitation of clinics.
It was with the appearance of Vaniqa that a solution began to take shape. As Aventis was threatening to drop its panel of HAT drugs, BMS was examining new uses for failed drug candidates and found that DFMO in a cream preparation enabled hirsute women to eradicate facial hair. Topical application eased the problems of administration in a resource-poor setting and existing production facilities could be used as the source. Jannin's group persuaded BMS to donate the drug for five years, and additional lobbying triggered Aventis and Bayer to continue producing the other HAT drugs, and donate US $5 million a year for five years for monitoring, treatment and research and development.
The result is current widespread access to a much-needed drug. 55 million people are exposed to HAT in 36 countries, with only 4 million of those under surveillance. There are half a million new cases a year, with perhaps 60,000 deaths, according to estimates by the World Health Organization (WHO). By contrast, the rate of disease in 1960 was 1 or 2 per 10,000.
