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Why a Gates Foundation Gift Was Not Enough for Haiti's Children

The post-earthquake horror in Haiti and the nation's desperate need for aid, as we learn from Presidents George W. Bush and Bill Clinton, is not going away anytime soon. For me, the area of greatest concern is the Haitians' lack of access to clean drinking water. The repercussions go far beyond immediate enteric infections like life-threatening cholera, severe diarrhea (the No. 1 killer of children under age 5), and dehydration, also posing long-term threats to the physical health, cognition and human rights of Haiti's people. Before the quake, 47 percent of Haiti's residents had no access to clean water, while two-thirds lived without adequate sanitation. I heard a leading refugee coordinator call this situation a "weapon of mass destruction."

A potential tool in the armament against the devastation of dehydration is crofelemer, a pharmaceutical product derived from the knowledge of shamans, or healers, in the South American rain forests. The existing go-to formula, Oral Rehydration Solution (ORS), does indeed replenish depleted bodies and save lives, and should always be given to children and patients with severe disease in the case of dehydration. ORS does not slow or stop water loss. A complementary approach, crofelemer, according to data presented at scientific conferences, decreases fluid loss, and shortens the duration of diarrhea in both the mildest and most severe of cases, including cholera and chronic diarrhea in immuno-compromised patients.

Crofelemer has been in discovery and development as a pharmaceutical product for nearly 20 years. A targeted product launch for adult indications in several countries is 12 to 24 months away, pending final studies and regulatory approval. Its pharmaceutical developer is committed to providing global access--all countries, all populations and all channels of distribution, regardless of social or economic status--to the ultimately approved product.

Enter angst: The development of crofelemer could have already been complete, including an investigation into its use in pediatric populations in combination with ORS (and zinc, another beneficial intervention). As I watch newscasts of the destruction in Haiti, images flash through my mind of all those who have hindered the investigation into crofelemer's promise, and thereby the possibility of making a life-saving medicine available in crises like the one in Haiti.

Here's the story: In 2001, the investigation of crofelemer for pediatric populations was the subject of a potential grant from the Bill & Melinda Gates Foundation, under which the developer--which had initiated the partnership in an effort to ensure that the product would be available to those most in need--would donate crofelemer to resource-constrained areas of the world. The developer was told that the grant would have to go through a nonprofit organization for tax reasons, so it chose the San Francisco-based Institute for OneWorld Health (iOWH) because of its focus on childhood disease and its interest in funding activities not otherwise pursued by the pharmaceutical industry.

Almost three years and hundreds of thousands of dollars in legal fees later, terms were agreed upon and a contract was drawn up for a grant totaling tens of millions of dollars. Near the end of 2003, the Gates Foundation informed iOWH and the developer of its desire to move money for the crofelemer project--more generalized to its novel mechanism of action to address water loss, termed a CFTR-inhibitor project--to iOWH by Dec. 31 for tax purposes. The foundation sought assurances from the developer and iOWH that the contract was ready to be signed. In good faith, it was. The money moved to iOWH. Then, in a surprise year-end move, iOWH informed the developer that it was tired of living off Gates Foundation grants and wanted some private market compensation. This meant that in addition to donating crofelemer for pediatric purposes, the developer would have to compromise its intellectual property position to provide private market return to iOWH in order to access the crofelemer-designated grant funds. Shortly thereafter, the principals at iOWH went on vacation.

A leading academic investigator called the actions of iOWH "unethical, even for a for-profit company (which iOWH is not). In 25 years on the faculty at [a leading academic institution] and dealing with multiple companies and collaborators, I have not been witness to such inappropriate behavior." The developer walked away from the situation, noting the worthy intentions of both parties, and citing the lack of a culture match to consummate a successful collaboration at that point in time, yet leaving the door open for future discussions about efficiently bringing crofelemer to pediatric populations, should it meet regulatory approval. iOWH kept the grant money and did not inform the Gates Foundation of the breakdown of the potential alliance for several months.

Despite being close to broke, the developer was able to move forward with innovation in the pharmaceutical business model, partnering with local companies and allying with relief efforts to ensure sustainable development of crofelemer and its ultimate availability to the global health community upon regulatory approval, independent of eleemosynary agendas. Investors with great vision supported this effort for social change in the pharmaceutical industry, venturing beyond their traditional comfort zones, and top international experts in the field of diarrhea research participated in the investigation of crofelemer.

So what happened to the grant money? iOWH spent almost four years seeking early-stage technology that met the CFTR inhibitor definition criteria for the cash that was presumably sitting in its bank account, several times issuing PR announcements about its "campaign to jump-start research on diseases of the developing world that haven't been addressed by for-profit drug companies," and professing it had "seized the initiative in recent years to clear logjams in the drug development process that the industry hasn't overcome."* iOWH's pronouncements confused global health experts, who pointed to the presentation of clinical data on crofelemer at scientific conferences throughout the years. In an interview with the San Francisco Chronicle in April 2008, iOWH claimed it would bring a proof of concept CFTR inhibitor to the clinic in six and a half years. The Chronicle refused to correct the misleading message.

Normally, in the drug industry, a pediatric product is developed subsequent to safety and efficacy testing and approval in adults. Over the years--most recently one day after the earthquake in Haiti--the developer of crofelemer reached out to both iOWH (the management of iOWH has changed) and to the Gates Foundation, proposing joint efforts to accelerate the development of a pediatric crofelemer. To the astonishment of those who witnessed the discussions, the developer was rebuked by both.

Crofelemer's first-in-class status is important to the pursuit of approaches to mitigate diarrhea and dehydration. In the best case, crofelemer would have already been successfully developed and would be distributed in Haiti today as the country struggles to organize sufficient infrastructure to help its people and, in particular, its children--the next generation. Even if crofelemer had not lived up to its promise, that knowledge would have expedited an efficient deployment of resources to direct future drug development efforts, as President Clinton noted during the 2009 Clinton Global Initiative conference, which highlighted a commitment to global access to crofelemer. It's frustrating, and ironic, that the important shared focus of the Gates Foundation and iOWH--mitigating diarrhea in children, particularly with the novel mechanism CFTR inhibitor--has hindered this investigation and delayed the potential introduction of such a product to the global health community.

With great gifts comes great responsibility. No doubt, the Gates Foundation is a profound gift to global health, accounting for 80 percent of NGO funding these days. A Gates grantee recently told me that when, due to the recession, the foundation didn't increase its grant funding this past year, the effects were felt thunderously by the NGO community. In many arenas of global health, the foundation is the agenda.

The crisis in Haiti and the helplessness we all feel have moved me to write to the Gates Foundation again, yet perhaps this time in a way in which the message won't get submerged by those with personal agendas to protect at all costs, the most precious of which are the lives of children in places with little resources. Dear Mr. Gates, I hope you get this message.

Napo Pharmaceuticals, Inc., press releases: "Napo Gathers International Panel on Global Health," Oct. 8, 2009; "Napo Announces Positive Clinical Data Indicating Crofelemer Could Effectively Treat Cholera," Sept. 22, 2008; "Napo Announces Successful Clinical results in Phase 2 Study of Crofelemer in Acute Adult Infectious Diarrhoea," April 10, 2008
"Napo Pharmaceuticals," Stanford Graduate School of Business case study by Joshua Spitzer, May 18, 2006.
Letter to Tadataka Yamada, President of the Global Health Program at the Bill & Melinda Gates Foundation, Jan. 16, 2008.
Letters from and to Ahvie Herskowitz, COO of Institute for OneWorld Health, and Lisa Conte, CEO of Napo Pharmaceuticals, Inc., March/April, 2005
Wired News, "A Drug to Eradicate Diarrhea," Kristen Philipkoski, July 11, 2005.
Letter to the Editor of the San Francisco Chronicle from Conte in regards to "OneWorld teams with Roche for diarrhea cure" by Bernadette Tansey on April 17, 2008.
Email from Conte to Yamada, Jan. 2008
The Lancet, "The Bill & Melinda Gates Foundation's grant-making programme for global health," D. McCoy, G. Kembhavi, J. Patel, A. Luintel, vol. 373, issue 9675, May 9-15, 2009, pp. 1645-1653.