CHAPTER SIX – Healthy: The Institute For Oneworld Health

Talk about social hybrids!

Ask people to list big, profit-hungry businesses, and you’ll likely hear the names of firms within the pharmaceutical industry. Worldwide, we spend approximately two-thirds of $1 trillion on prescription drugs every year, with the United States accounting for nearly half that amount. Watch television for a few hours, and the commercials that bombard you will let you know what drug companies seem to say we need most: drugs with attractive colors (especially if taken while dancing in a field of flowers) and drugs that can enhance your, ahem, physiology.

Then along comes the Institute for OneWorld Health, the world’s first nonprofit pharmaceutical company, focusing on neglected infectious and parasitic diseases that affect the poorest parts of the world.

OneWorld Health is redefining the pharmaceutical industry’s beliefs about how these conditions can be addressed. By adopting Big Picture Design—very Big Picture Design—it has come up with various drug “discovery” methods that can put tropical diseases primarily affecting the world’s poor within the sights of the industry. OneWorld Health’s intention is to get badly needed medicine to large numbers of people with serious illnesses who have never been able to afford it.

If you were looking to climb mountains, you’d be much better off going to Switzerland than Kansas: that’s where mountains are. And, of course, climbers do flock to the Alps. So, if you are looking to fight diseases, why not go where the most critical diseases are? Sadly, health care dollars rarely make it there.

Consider the Disability Adjusted Life Year, which measures the loss of productive life because of premature death and disability to compute a measure of overall health burden. By this measure, 90 percent of the burden is in the developing world, yet only 10 percent of all health dollars are spent there. In all, one-half of the people in the poorest regions of Africa and Asia have no access to essential medicines.

New and affordable medicines are certainly called for to treat the diseases that afflict such regions. Yet in the twenty-five-year period ending in 1999, less than 1 percent of the nearly 1,400 new drugs developed were targeted at tropical diseases that wreak havoc on the lives of the poor.

Of course, the explanation for these lopsided statistics is that health care follows the money,rather than disease. “Of course”—but only if pharmaceutical companies are consumed by the idea of making a big profit.

But they don’t have to be. That’s what Victoria Hale concluded when she founded OneWorld Health. Instead, it is possible for a pharmaceutical company to make improving health its dominant focus. By Picturing the Design of the organization she wanted to build in this Enormous (not just Big) way, Hale threw off the shackles that restrict the ways that ordinary pharmaceutical companies approach business.

Hale, with a PhD in pharmaceutical chemistry, and stints in industry and the Food and Drug Administration’s Center for Drug Evaluation and Research, was intimately acquainted with conventional drug development. She had worked in biotechnology and knew of its promise for drug discovery. She also knew that the bill for modern drug development comes to $800 million per drug. And that only one in 100,000 drugs makes it to market, most proving to be ineffective in clinical trials. Even then, 70 percentof the drugs that reach the market never recoup their investment.

It might be rational for pharmaceutical companies that are focused on making stockholders wealthy to strive only to develop blockbuster drugs, whether they appeal to our vanity or address serious health concerns such as diabetes or heart disease. Despite the cold, hard numbers, Hale still felt outraged that almost no effort was being made to address the tragic illnesses associated with being desperately poor.

But what could she do?

Big Picture Design

Hale founded the Institute for OneWorld Health to focus on furnishing affordable drugs to extremely poor people suffering from infectious, parasitic, or tropical diseases. She designed OneWorld Health to be a nonprofit so that it can operate with an entirely different set of business processes than a traditional drug company. But rather than basing its efforts on a bankroll of hundreds of millions of dollars, OneWorld Health relies on other resources: brains, partnerships, and the stuff in people’s attics.

Well, not their attics exactly. But just as old trombones, prom dresses, and vinyl LPs that you just know you’re going to listen to again—someday—end up in the attic, drugs that don’t make it to market, go out of patent, and make it only partway through clinical trials end up somewhere musty, too. For Hale, discarded drugs can be attic treasures.

The first drug for which OneWorld Health obtained regulatory approval was an injectable antibiotic called Paromomycin IM for the disease visceral leishmaniasis. VL or “black fever” is the second-most deadly parasitic disease in the world and is fatal, killing 300,000 people a year. By the time OneWorld Health came on the scene, the VL parasite had become resistant to the active element in the most common drug, another treatment required inpatient hospitalization, and a third cost $100 per treatment. None of these was an acceptable option.

OneWorld Health found Paromomycin in the attic of the World Health Organization. Was Paromomycin untested, ineffective, or unsafe? Did it produce debilitating side effects? No, no, no, and no. The injectable drug had been developed in the 1970s by Pharmacia, a drug company that merged with the drug giant Pfizer in 2003. Paromomycin had proven to be an effective antibiotic but was shelved by Pharmacia when more convenient oral antibiotics became available. The World Health Organization (WHO) obtained the rights to the drug and began considering using it to treat VL, against which it was highly effective. The WHO even conducted midstage clinical trials but then abandoned its effort to bring the drug to market for budgetary reasons.

OneWorld Health obtained a joint license for the drug from WHO. Because much of the clinical effort (and expense) had already been borne by WHO, the demands on OneWorld Health to get the drug to market were greatly reduced.

OneWorld Health designed and conducted late-stage clinical trials of Paromomycin in Bihar, India, an extremely poor region where 100 million people are at risk for VL. Clinical trials took four years, and in August 2006, the injectable antibiotic received regulatory approval from the Indian government.

There is a vast warehouse of discarded drugs because of expired patents, their side effects, and, simply, better alternatives. Although these discards are attractive to OneWorld Health, they present a nice opportunity for pharmaceutical companies, too, who can license them to OneWorld Health and receive tax deductions based on their future revenues.

But scouring others’ attics is not the only means OneWorld Health uses to find drugs that can treat orphan diseases. Remember, OneWorld Health is a master at Big Picture Design, which includes using any means possible to make societal advances. And OneWorld Health has two other key resources at its disposal: brains and partnerships.

OneWorld Health is in the process of combining one of the world’s oldest approaches for treating malaria with cutting-edge science and bioengineering. Malaria is a scourge of the developing world, especially in sub-Saharan Africa but also in India, elsewhere in Asia, and in Latin America. Malaria is an infectious disease transmitted by mosquitoes, which can cause severe illness or death if not treated. Children and pregnant women are highly susceptible to the disease. Someone dies of malaria every thirty seconds.

Two thousand years ago, Chinese healers discovered the herb sweet wormwood could be used to treat malaria. In the 1970s, Chinese scientists discovered the active ingredient in this herb: artemisinin. Low-cost, commonly used drugs to treat malaria have lost their effectiveness as the parasite that causes the disease has mutated to gain resistance to these drugs. But artemisinin, in combination with other drugs, is quite effective. What’s more, because the drugs are used in combination, drug resistance is less likely. But artemisinin combination therapy is still too costly for most patients, although it costs only $2.20 to treat one bout of malaria.

Artemisinin costs $900 per kilogram, contributing more to the cost of artemisinin combination therapy than any other factor. Further, artemisinin grows only in certain locations, takes time to grow, and is affected by the weather. It is also time-consuming to extract the proper chemical ingredients from the plant. These factors affect its availability, reliability, and purity.

In 2004, OneWorld Health set out to produce artemisinin more reliably, with greater consistency, and at a far lower cost by using synthetic biology. A partnership between OneWorld Health, the University of California, and the drug company Amyris Biotechnologies successfully determined how to extract the appropriate genes from the sweet wormwood plant and insert them into the bacteria E. coli. to cause a chain reaction of chemical processes that produces artemisinic acid. This acid is then obtained from the bacteria and converted into artemisinin using a novel chemical process. This process takes days compared with months for artemisinin to be grown, harvested, and extracted from plants.

At present, the scientists working on the Artemisinin Project have shown that the synthetic biology approach can work. What is still needed is further refinement to optimize the approach to ensure that it can be employed on a commercial scale. They must also demonstrate that synthetic artemisinin is as effective as artemisinin harvested from plants; if so, they can forgo clinical trials and can begin to use it in the field.

In 2008, the pharmaceutical company Sanofi-aventis became a member of the Artemisinin Project. Its chemical process expertise is fundamental to producing synthetic artemisininin commercial quantities. Hopes are that synthetic artemisinin will become widely available by 2012, eventually treating up to 200 million malaria patients a year (approximately 40 percent of demand), with a reduction in artemisinin combination therapy costs possibly reaching 90 percent.

By scouring the attic to find a drug for VL as well as using state-of-the-art biology and chemistry to develop a way to attack malaria, OneWorld Health clearly demonstrated its adherence to one of the main principles of Big Picture Design: looking anywhere and everywhere for ideas that work and then stealing shamelessly. But another tenet of Big Picture Design is ensuring that all aspects of a societally beneficial business are taken into design consideration. Nothing should be left to pure chance. In this way, too, OneWorld Health exhibited Big Picture Design. Although it is a pharmaceutical company, OneWorld Health has no laboratories, nor does it have the capability to manufacture drugs or deliver them to where they are needed. But just as collaborations were essential in the “discovery” of synthetic artemisinin, partnerships are the force behind OneWorld Health making drugs and getting them to patients.

OneWorld Health partnered with the U.S. firm Odyssey Research to conduct its last-stage clinical trials for the VL drug Paromomycin. And it partnered with Gland Pharma, a firm in Hyderabad, India, with expertise in injectable drugs, to produce Paromomycin for the market. Gland agreed to make the drug at cost, approximately ten dollars for a lifetime cure for this fatal disease.

A VL patient being treated with Paromomycin requires one injection a day for three weeks. That would be a very tall order for someone in the United States who has a car and a health facility nearby. How do you manage this in desperately poor places such as rural Bihar, India, where traveling to the nearest health facility can be a long, arduous journey, often made on foot, and made worse by the fact that the people who undertake it are so sick?

OneWorld Health partnered with the Indian organization Janani, a nonprofit that harnesses market forces to bring reproductive health and family planning services to the rural poor in Bihar. Janani has established a series of 620 franchised health clinics and 31,000 health shops in the region that are connected to its central clinic, thereby creating a dense health-delivery network. In each of these for-profit clinics and shops, Janani provides appropriate training and financial incentives for rural health providers to deliver reproductive and family planning services and products and to make referrals to doctors for more advanced clinical services.

OneWorld Health is piggybacking on this rural medical infrastructure to make sure that those needing Paromomycin can get it. Rural health providers are being trained to diagnose VL and provide injections. But, there is still the problem of compliance: patients need injections twenty-one days in a row for the treatment to be effective. How do you make sure patients show up for their required treatments?

In the West, the informational aspects of this problem would not be too difficult. A database in a doctor’s office or clinic could track patient compliance (or lack thereof), easily monitoring patients’ injections. But a Janani health center may be run out of someone’s home or be part of a lean-to “store” where the chance of using computerized medical record keeping is as unlikely as finding a four-star restaurant.

OneWorld Health approached another social hybrid, Voxiva, seeking help for its data-tracking needs. Voxiva has a suite of technologies that can be used to track epidemics in real-time, even when there is extremely limited access to information and communications technology infrastructure. In its support of OneWorld Health, Voxiva established a system of text-message alerts to help monitor compliance. Rural healthcenters send a text message to Voxiva every time a patient receives an injection, letting Voxiva know the patient’s identity. Voxiva, in turn, records and compiles this information and sends text-message alerts to centers, letting them know which of their patients are due for injections on a given day. This allows the centers to contact any patients who fail to show up and follow up. In this way, centers can deal with the informational complexities of treating many patients for VL, each of whom is at a different point on the twenty-one-day treatment schedule. And, as important as it is for patients to receive all their injections for treatment to be effective, ensuring this behavior and recording the results is also vital for the last-stage clinical trials in the field to demonstrate the efficacy of the injectable antibiotic Paromomycin.

Making It Appropriate

Clearly, OneWorld Health places a premium on Making It Appropriate. The essence of Making It Appropriate is being certain that the right combination of factors—the right context—is in place. Looking through inventories of discarded or out-of-patent drugs for those that might be used in the developing world is, really, nothing more than trying to find another context in which they might be useful.

Even a drug’s side effects are a matter of context. Rogaine was introduced as a blood pressure medication. But voilà, when scientists noted it produced a common side effect—hair growth—this became its main effect when it was reintroduced as a product for baldness. Viagra was initially introduced as a heart medicine. Medicine that is thrown in a Western drug company’s attic because it makes patients sleepy may be perfectly acceptable in the context of treating a serious disease in the developing world.
Inappropriate often means too costly or inaccessible. As we have already seen, much of OneWorld Health’s attention to design is aimed at preventing such possibilities. That is what its mission is all about.

Making It Stick

Even when you have thought expansively by using Big Picture Design and have tried to do all you can to Make It Appropriate, there is still your acid-test, rubber-meets-the-road, moment of truth: Will your product or service be accepted? In other words, will it stick?
OneWorld Health aimed to ensure it would, by many of the decisions it made. The selection of Bihar, India, as the site for introducing Paromomycin could be justified on the grounds that visceral leishmaniasis was rampant there. But just as important was that the vast number of Indians without access to health care made it possible to more quickly recruit large numbers of subjects for clinical trials and get regulatory approval.
the idea that getting regulatory approval from the Indian government, rather than another, might hasten the process of getting the new antibiotic into wide-scale use. But gaining governmental approval and a community’s acceptance are very different matters.

Victoria Hale described the “Constant Gardener” factor in Bihar when OneWorld Health went there to conduct its clinical trials. The phrase refers to the film The Constant Gardener, which depicts how an unscrupulous drug company takes advantage of the poor people of Kibera (the Nairobi slum that, I hope you recall, was the location for Enterprise for a Sustainable World’s work with SC Johnson on the Base of the Pyramid Protocol). The people of Bihar were wary of OneWorld Health. Would they be exploited? What did the company really want to accomplish in Bihar? By making its health-focused mission 100 percent clear and working continually to build trust, OneWorld Health was eventually able to get a toehold in the region. This trust was an essential first step in Making It Stick.
The hub-and-spoke health delivery model of Janani was equally vital to create lasting success. (The nonprofit Janani served as the “hub” that provided substantial business benefits for the thousands of small for-profit clinics and health shops connected to it by “spokes.”) By partnering with Janani and embedding its efforts in the Janani network, OneWorld Health created the means for Paromomycin to be safely administered over the long course.

Even OneWorld Health’s financial decisions contributed to its efforts taking off. OneWorld Health chose to pay the development costs associated with the first batches of Paromomycin in agreement for its partner, Gland Pharma, producing and selling Paromomycin at cost.

Making It Bigger

Upon its founding, when OneWorld Health sought nonprofit status, the Internal Revenue Service resisted. To the IRS, the equation
nonprofit + pharmaceutical company = new hybrid form
didn’t make sense. Today, the idea not only makes sense but its impact is spreading.

In 2007, the Paromomycin IM injection was put on the World Health Organization’s Model List of Essential Medicines. Essential medicines are those that address the most important public health needs of the population. The Model List is based on a drug’s quality, efficacy, and safety. The WHO declared that Paromomycin was “most cost effective among all available alternatives,” thus adding it to its Model List. By its inclusion on the Model List, Paromomycin is intended to be made available by health agencies in regions where VL is prevalent and by agencies such as UNICEF that address health care needs worldwide.

OneWorld Health is Making It Bigger in other ways, too. Seeing what OneWorld Health has accomplished has begun to make other institutions rethink their own roles as well. Hale has received more than a hundred proposals from pharmaceutical companies and academics wanting to get involved, thus greatly expanding OneWorld Health’s resource base of brains and partners.

New types of institutions are being contemplated to complement the kinds of efforts that OneWorld Health makes. For instance, the Tropical Disease Initiative was established in an effort to create an “open-source” approach for drug development. Working collaboratively over the Internet and using computational methods that are beginning to replace the “wet science” of the biological lab, volunteer scientists address problems related to neglected tropical diseases, share data, and begin to suggest new solutions. This kind of effort could become an attractive pipeline for OneWorld Health in its attempt to select the best of these and bring them to market.