Bill & Melinda Gates Foundation Awards $4.6 Million to Institute for OneWorld Health for Drug Development in Fight Against Neglected Insect-Born Diseases

SEATTLE AND SAN FRANCISCO -- As an infectious disease outbreak raises public awareness and concern in the U.S., the Bill & Melinda Gates Foundation today announced two new grants totaling more than $4.6 million to the Institute for OneWorld Health (iOWH) to fund drug development that will treat two parasitic, neglected diseases – visceral leishmaniasis and Chagas.

iOWH today announced a $4.2 million grant from the foundation to begin final testing of paromomycin, a promising new therapy to cure visceral leishmaniasis, a deadly parasitic disease threatening more than 350 million people worldwide.  Also today, iOWH said it will receive a $476,100 grant from the Foundation to complete pre-clinical testing of K-777, a new drug designed to fight Chagas disease, which kills an estimated 50,000 people annually in Latin America and afflicts more than 16 million worldwide. 

"The West Nile outbreak reminds us all that that we are interconnected across borders and oceans, and that we must never neglect efforts to prevent these infectious diseases," said Sally Stansfield, M.D., Acting Director of Infectious Disease and Vaccines Program for the Bill & Melinda Gates Foundation.  "The foundation is committed to projects such as those at iOWH that focus on the prevention and control of infectious disease.  We are working to build coalitions among scientists, universities, nonprofit agencies and private industry to ensure that new drugs are developed and deployed.  We are pleased to support this unique research collaboration."

Visceral Leishmaniasis
This grant will enable iOWH to partner with the World Health Organization's Special Program for Research and Training in Tropical Diseases (WHO/TDR) and the International Dispensary Association (IDA) to develop paromomycin as a new anti-parasitic drug therapy for visceral leishmaniasis.   Following completion of a single large Phase III clinical trial, iOWH and its partners will seek regulatory approval of the drug in India.

"Most Americans think of pinworms or problems with their dogs or cats when they think of parasitic diseases," said Dr. Jere Goyan, former Commissioner of the Food and Drug Administration (FDA) and Dean Emeritus of the School of Pharmacy at the University of California, San Francisco. "Most do not realize that there are so many parasitic diseases that inflict suffering and hardship on the people of developing countries."

About leishmaniasis
Leishmaniasis is recognized by the World Health Organization as a "neglected" disease – one that has particular impact on the world's most vulnerable populations, but receives little funding or public attention.  With a mandate to develop drugs for such neglected diseases, the Institute for OneWorld Health has made leishmaniasis a priority for its drug development efforts.

Leishmaniasis is a parasitic disease transmitted by the bite of a sand fly, a tiny and often unrecognized threat.  Leishmaniasis is found in 88 countries, and the disease afflicts over 12 million worldwide.  Four major forms of the infection are known, but the most lethal form of the disease is visceral leishmaniasis. 

Also known as "black fever" or "kala azar", visceral leishmaniasis infects 500,000 annually, and is responsible for 60,000 deaths each year.  Ninety percent of all cases occur in five countries: India, which has the greatest burden of the disease, Bangladesh, Brazil, Nepal and Sudan.  Left untreated, the visceral form of leishmaniasis is universally fatal. The disease typically affects children and young adults in the poorest populations. The incidence of visceral leishmaniasis is increasing rapidly, particularly among people with immune systems compromised by malnutrition and HIV infection. 

"Visceral leishmaniasis has traditionally preyed on impoverished segments of the population, especially children," says Dr. Victoria Hale, founder and CEO of  iOWH. "Increasing urbanization aids the parasite's introduction into new and more densely populated communities.  Recent epidemic outbreaks of visceral leishmaniasis in Sudan and India serve as warnings that the disease is on the move, and threatens already overburdened health systems throughout the developing world."

The onset of visceral leishmaniasis is characterized by irregular bouts of fever, substantial weight loss, swelling of the spleen and liver, and anemia.  Progressively malnourished and immunocompromised, these patients face the threat of co-infection with pneumonia and tuberculosis. Without intervention, the mortality rate for visceral leishmaniasis is near 100%.

Paromomycin, which has proven highly effective against visceral leishmaniasis in Phase II clinical testing, is a powerful new addition to the drug armamentarium.  Paromomycin will be affordable, shows no signs of parasite resistance, and is anticipated to have limited safety concerns.  Because the majority of visceral leishmaniasis occurs in India,  iOWH and WHO/TDR will conduct the paromomycin trial in the state of Bihar (in NE India), partnering with physicians at four kala azar/black fever hospitals in Patna and Muzaffarpur to complete the clinical trial.

"This testing program in India will contribute to building the capacity of laboratories in developing countries," says Dr. Carlos Morel, Director of the TDR program of tropical disease research. "It is vitally important that research and testing are carried out in the countries most affected by infectious diseases.  This is a great example of how it can be done."

 iOWH will co-develop paromomycin with international development, manufacturing and distribution partners, including the WHO/Tropical Disease Research Unit (Switzerland) and the International Dispensary Association (the Netherlands).  This unique global consortium will complete the clinical trial in India and register the drug in India, Bangladesh and Nepal.  In order to promote transfer of technology, the iOWH and its partners will identify a manufacturer in India to produce the drug.

Chagas Disease
K-777, a protease inhibitor, could be the first new therapy against Chagas disease in over half a century.   In a unique collaboration between a biopharmaceutical company and a nonprofit organization, Celera Genomics Group, an Applera Corporation business, granted the iOWH development rights to the new anti-parasitic drug. 

"Diseases such as Chagas present unique challenges in drug development," said Kathy Ordonez, President of Celera Genomics.  "We applaud iOWH's undertaking and are proud our research may in some way contribute to a cure for this disease."

Through this grant from the Bill & Melinda Gates Foundation and with support from the National Institute of Allergy and Infectious Diseases (NIAID), iOWH will complete pre-clinical animal testing to enable initial human testing of K-777.  iOWH will then file an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA).   iOWH expects to begin Phase I clinical trials in healthy human volunteers in about two years.  iOWH will seek international partners to develop K-777 for Phase II and III clinical trials in South America if Phase I results are promising.

About Chagas disease
Chagas disease is recognized by the World Health Organization as a "neglected" disease – one that has particular impact on the world's most vulnerable populations, but receives little funding or public attention. Endemic to 21 Latin American countries, Chagas disease is a major cause of heart failure in the region. Chagas disease is caused by the parasite Trypanosoma cruzi, transmitted to humans by an insect commonly known as the "kissing bug", and by tainted blood transfusions.  Both humans and many varieties of domestic and wild animals can carry the parasite, and the insects infected with T. cruzi often live in the thatched roofs and walls of houses.

Chagas disease has both short and long-term effects. The acute effects appear soon after infection and are generally seen in children. Symptoms can include fever, swelling at the site of the insect bite and of the lymph glands, and enlargement of the liver and spleen. The long-term effects can occur up to 20 years after infection.  During the chronic phase of the disease, the parasite causes irreversible damage to internal organs such as the heart, esophagus and colon. Patients with these late-stage effects become progressively more ill and then die, usually from heart failure.

"In 25% -30% of those infected, Chagas disease is a slow and insidious killer, attacking the heart or gastrointestinal tract over decades," says Dr. Dan Colley, a professor of infectious disease at the University of Georgia and former Director of the Division of Parasitic Diseases at the Centers for Disease Control and Prevention (CDC).  "No available drug has been shown to consistently cure patients in this chronic phase.  The availability of such a drug would dramatically change how Chagas disease is managed in the clinic and in the community."

Current treatments for Chagas disease have substantial drawbacks because patients face a tradeoff between efficacy, safety, and affordability.  "There is no question that new drugs need to be developed," urges Dr. Colley. "The drugs currently available to treat this life-threatening infection leave much to be desired.  They are often ineffective in curing the infection, especially when used for the vast majority of patients who have long-standing chronic infections.  They are difficult to administer and are also quite toxic, leading to severe side effects in adults.  It would be a major advance in public health if a safe, efficacious, easily administered and reasonably priced drug were to be developed."

About the Institute for OneWorld Health
The Institute for OneWorld Health (iOWH) is a nonprofit pharmaceutical company whose sole purpose is to develop affordable, new drug treatments for neglected infectious diseases in the developing world.  iOWH's primary target is parasitic disease affecting the developing world, for which there are currently no therapies or inadequate therapies. Comprised of pharmaceutical scientists with international drug development and regulatory expertise, the iOWH identifies promising drug candidates and executes preclinical and clinical development of drugs, with the goal of regulatory approval of new therapies in the most affected countries. The Institute was founded in July 2000, and is a tax-exempt 501c(3) not-for-profit corporation. 

On the Internet:

Institute for OneWorld Health, www.oneworldhealth.org
Bill & Melinda Gates Foundation, www.gatesfoundation.org