A World Away
by Sarah Fister Gale
October 2008
Finding solutions for the neglected tropical diseases that affect one billion people worldwide requires not only a commitment to conduct sorely needed research, but also a rethinking of drug development’s value proposition.
Photography by Sam Diephuis/zefa/Corbis
In a world where billions of dollars are spent annually on research in pursuit of a better diet pill, there is a category of woefully neglected tropical infections, such as visceral leishmaniasis, diarrheal diseases and Chagas, that threaten the lives and livelihoods billions of people worldwide.
Despite the need for drug research into potential treatments for these illnesses, few major pharmaceutical companies include tropical diseases among their research portfolios. Often, the populations that suffer from these diseases have no money and cannot pay even small premiums for new drugs, which means even if a treatment is discovered, the manufacturers will likely have to donate them for free.
“Although [these diseases] represent the vast majority of human morbidity and mortality, the development of drugs to treat them has been almost moribund for several decades,” notes Dr. Timothy Coté, director of the Office of Orphan Products Development for the U.S. Food and Drug Administration (FDA), in Washington D.C., USA. “The principle reason for this has been economics: There has been little incentive to invest in the costly endeavor of drug development to make products for people without the means of purchasing them.”
Development and Distribution
In addition to a lack of financial incentives, other obstacles hinder development and delivery of solutions to these illnesses. A lack of infrastructure, poor health education and no driving force behind these causes have all contributed to global apathy about the world’s most fragile populations.
“There is no risk to the people in the EU, the U.S. or Japan to contract these diseases, so it’s more difficult for them to get attention,” says Dr. Jean Jannin, coordinator of innovative and intensified disease management and neglected tropical diseases control for the World Health Organization (WHO) in Geneva, Switzerland.
“Even though these are the most common disease conditions of all humankind, they are classified as ‘orphans’ because they meet the definition, as set out in the Orphan Drug Act, of having fewer than 200,000 people with the disease here in the U.S.,” Coté adds.
Even if pharmaceutical companies do commit the time and resources to develop treatments, conducting clinical trials in the regions where these diseases occur is extremely difficult, as patients are hard to reach and few facilities exist in which the research can be conducted.
Distribution of drugs and diagnostics poses the final, significant challenge, because many patients live in deeply remote areas with no transportation network or distribution system in place. “It’s not even enough to have a drug available free of charge, you also have to ensure access to treatment for the patient,” Jannin says. “If you invest millions to develop a drug, the risk that it cannot be properly distributed is still present.”
Despite these seemingly insurmountable hurdles, the attitude toward these diseases is slowly changing as pharmaceutical companies begin to see the value of corporate social responsibility programs, and governments commit more attention and resources to improving world health conditions.
Why Partnerships Work
The key to approaching these diseases is that no one government, pharmaceutical company or not-for-profit organization can do it alone. It takes a synergistic network of groups, each contributing their own knowledge, technology, manpower and expertise, to create a multi-dimensional solution that can first create treatments, and then get them to the people in need.
The recent collaboration to find a treatment for diarrheal disease between The Institute for OneWorld Health, a non-profit pharmaceutical company in San Francisco, Calif., USA, and Roche Pharmaceutical, the global pharmaceutical company, is an excellent example of how disparate groups can work together in cost effective ways to discover solutions that could not be accomplished individually.
Diarrheal diseases kill approximately 2 million children under the age of five in developing countries every year—exceeding the pediatric death toll of AIDS, tuberculosis and malaria combined.
Through its Diarrheal Diseases program, OneWorld Health is working to discover and develop a novel anti-secretory diarrheal drug to reduce fluid loss and help prevent death from dehydration caused by acute watery diarrheal disease. This treatment is intended as an adjunct to Oral Rehydration Therapy (ORT) and zinc to save the lives of infants and children.
To support that goal, in April 2008 Roche opened its library of compounds to OneWorld Health researchers, allowing them to screen the compounds in hopes of identifying a potential new drug for the treatment of diarrheal diseases. “We really hope that by making these resources available to OneWorld Health, they find a treatment for this disease,” says Jacqueline Wallach, vice president of communications for Roche.
By granting OneWorld Health access to its compound library, it’s done more than make a financial contribution, notes Susan Wilson, senior program director for the Diarrheal Diseases Program with the Institute for OneWorld Health. “You can’t put a dollar value on it, but the potential payback is huge,” she says. “We could create something that no single entity can do alone, and the impact of that is enormous.”
This kind of payback—in which OneWorld Health benefits from Roche’s experience and a knowledge base that could potentially lead to a new drug, and Roche could ultimately share in the credit for that drug—exemplifies how these partnerships are mutually beneficial.
It also reflects a change in how the industry is thinking about return on investment, Wilson says. “Our collaboration with Roche demonstrates more than a possibility for a solution. It will drive innovative thinking, and we can create a win-win situation in which profit doesn’t have to be the goal.”
Wilson says many large pharmaceutical companies are starting to rethink their business models and incorporating corporate social responsibility goals into the overall business structure. “Being able to contribute to these kinds of efforts makes a huge difference. If they can balance that with their core business strategy, it’s an attractive proposition,” she says.
Wallach agrees, adding that partnerships like the one Roche has with OneWorld Health tie into Roche’s core values. She points to other examples of Roche’s social investments, including donation of manufacturing for drugs to treat Chagas disease in Brazil; its support of local production of generic versions of HIV drugs in sub-Saharan Africa and less developed countries; and its diagnostics for infant testing for HIV in developing countries.
“Our collaboration with Roche is a testament to the significant change in thinking about these diseases,” Wilson says. “Several years ago this kind of partnership wasn’t possible. But today, many collaborations in the industry are going on right now that could positively impact the populations in these countries.”
Governmental Action
Other collaborations are being launched throughout the industry, from public/private partnerships among drug developers, to relationships between manufacturers and suppliers who can deliver the drugs. Governments and state agencies are also getting involved through programs such as the new Priority Review Voucher program launched by the FDA as a provision of the FDA Amendments Act of 2007.
The program offers a transferable “priority review voucher” to companies that obtain approval for a treatment for a neglected tropical disease. The program was designed to create market-based incentives to create new medicines for developing world diseases such as malaria, tuberculosis and African sleeping sickness.
The voucher has the potential to shave up to one year off FDA review, giving the manufacturer the financial incentive of an additional year on the market with a patent-protected drug while speeding access to highly valued treatments, benefiting patients and developers.
“The rationale behind the legislation has a very real basis in these neglected diseases,” Coté says. “This legislation seeks to change the economics by granting a financial incentive to developers of drugs for tropical diseases in the form of a valuable priority review voucher.”
Learning from Sri Lanka
It’s important to note, however, that none of these individual partnerships or incentive programs can create solutions by themselves. It requires a network of solutions that simultaneously create treatments, while developing the infrastructure and education to ensure they get in the hands of the people who need them, says Dr. Nilanthi de Silva, professor of parasitology at the faculty of medicine of the University of Kelaniya in Sri Lanka.
“It over-simplifies the problem to assume it’s just a matter of handing out medicines,” she says. “You can’t solve the problem just with drugs. You need to support the communities with education, sanitation and a strong health care infrastructure.”
De Silva points to the success Sri Lanka has had in reducing the incidence of certain infections thanks to a strong health care system, free education and well developed infrastructure to get the drugs to the people. “There are huge lessons to be learned from the investments we’ve made in health, education and female literacy since our independence in 1948,” she says.
De Silva also points to the dramatic reduction in hookworm infections. Because hookworm can aggravate anemia in pregnancy, a public health policy established in the early ’90s decreed that all women be given a dose of mebendazole during the second trimester of their pregnancies at local health clinics.
“Because 90 percent of women in Sri Lanka have their babies in hospitals, it was possible to determine that the treatment at the second trimester had no negative effects on babies,” says de Silva, who notes that the program also resulted in slightly higher birth weights.
Similarly, when infection rates were higher, children used to be treated for hookworm (as well as roundworm and whipworm ) once a year at school. “When the parents saw the positive effect the treatment had, they realized it made sense to de-worm their children,” de Silva says. “Even now, when infection rates are low and the treatment is no longer offered at most schools, parents ask about de-worming. It has become a sense of pride that it is good parenting to de-worm your children.”
The Last Mile
However, most countries that suffer from these diseases don’t have the infrastructure in place to launch such global campaigns. For many of these diseases, delivery of the drug and knowledge about treatment continues to be the hardest part.
OneWorld Health’s Wilson notes that in the developed world when a drug receives marketing approval it is considered a success. “That’s when the parties are thrown,” she says.
But in her world, marketing approval is only the first step. “For us, success is getting the drug to the people,” she says. “We literally have to think about how to go the last mile, because usually there are no roads and no infrastructure to cover that mile.”
She’s learned valuable lessons in this quest, which include taking the time to understand the culture and the business strategies of the community she’s trying to reach, and thinking creatively about covering the distance. “If you can get Coke and other products into a remote village, you can get drugs into the village; it just requires an understanding of the possible supply chain process or delivery networks.”
That may mean hitching a ride with a soda delivery truck, sending product in on motorbikes or partnering with local groups to travel the final stretch of road. “There is no substitute for feet on the ground and local knowledge on your team,” she says.
It is only by bringing everyone in the supply chain to the table, from the drug developers and clinical staff, to the infrastructure people, supply chain members and educators, that you can establish a common goal then build a plan to achieve it, Wilson says.
“Each member has an important contribution to make and together you can catalyze a virtual company to create synergistic interactions that you couldn’t do on your own. It’s just a matter of starting with the end in mind.”
Web Extra: Kids for World Health
Seven years ago, a group of nine-year old students from Larchmont, New York, USA proved that kids could make a difference. After an in-class viewing of a television segment on the lack of available treatment for sleeping sickness (trypanosomiasis) in Africa, the third-graders became activists. With the aid of an advisor, they organized Kids for World Health (KFWH), a not-for-profit organization dedicated to raising awareness and gaining funding for this cause. KFWH hasn’t lost momentum since: They now have branches in several cities and countries.
KFWH began by focusing on sleeping sickness —a disease that affects 500,000 Africans annually—and is 100 percent fatal without treatment. It is caused by a parasite and is carried to human beings and animals by the tsetse fly, an insect whose bite 60 million Africans are exposed to annually. The students were appalled to learn that medications to treat this sickness were available in the Western World, yet Africans lacked the resources to obtain them. Of the 60 million infected by the tsetse fly’s bite, just seven percent could afford the medication for treatment. Some of the drugs cost more than a person in Africa makes in a lifetime.
They decided it was time to do something, and wrote letters to numerous healthcare companies asking to help give assistance, monetary or otherwise, to contribute to eliminating sleeping sickness. The youth advocates were quite successful. They met with the CEO of Bristol-Myers Squibb, scheduled a trip to Washington, D.C. to lobby for access to drugs and raised thousands of dollars for the cause.
KFWH has since expanded its goals, focusing on raising further awareness of other neglected diseases such as Buruli ulcer, leishmaniasis and Chagas disease. They have initiated a number of projects to support this mission.
Since the birth of KFWH, there have been some strides made to combat sleeping sickness and other neglected diseases. After joint international efforts, sanofi-aventis made a five-year commitment to donate drugs to treat sleeping sickness. Others partners in this effort included Bayer and Bristol-Myers Squibb.
Although progress has been made, a long-term plan to combat these diseases has yet to be developed and many victims still do not receive proper care. KFWH vows to continue its mission until these diseases are eradicated, while also proving to the world that, regardless of age, people can make a difference when they work together.
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