GHIT Fund announces grants to speed up innovative drug development for neglected diseases

The Global Health Innovative Technology Fund (GHIT Fund), a new public health partnership that is bringing Japanese know-how and investment to the global fight against infectious diseases, today announced three grants worth a total of US$6.8 million to speed the development of innovative drugs for some of the world’s most neglected diseases—schistosomiasis, Chagas disease and parasitic roundworms. GHIT also announced a second round of funding of US$5.65 million for a novel vaccine candidate for tuberculosis and unveiled a new investment program that will help researchers find the most promising new drug candidates to battle these and other infectious diseases.

One billion of the world’s poorest people are afflicted with neglected diseases—also known as “the burden of the bottom billion”—and another three billion are at risk of being infected. Tropical disease infections, although not always fatal, can lead to delayed growth in children, impaired cognition and memory, malnutrition, organ damage, blindness, disfigurement and permanent disability.

“We're proud to support and push forward the development of three new technologies that target diseases that afflict over a billion people in the world,” said Dr. BT Slingsby, the CEO and executive director of the GHIT Fund. “The physical damage from these diseases is enormous, but that’s just the beginning. Victims are stigmatized by their communities, and because of repeated bouts of serious illness, they can’t provide for their families. The result is a never ending cycle of poverty that can and must be stopped.”

Testing for a Safer, More Effective Combination Therapy for Chagas Disease

The first grant, for US$3.84 million, goes to Switzerland’s Drugs for Neglected Diseases initiative (DNDi) and Eisai of Japan for a new combination therapy for Chagas disease, a parasite-borne disease transmitted by insects known as “kissing bugs,” named for the insects’ penchant for biting faces. Chagas kills more people in Latin America than any other parasitic disease. An estimated eight million people are infected, many unknowingly, leading to lack of treatment and heart or intestinal damage that could lead to death.

The current drugs for Chagas (benznidazole and nifurtimox) are poorly tolerated in adults, hard to use and frequently fail to cure chronic infections, which can cause cardiovascular disorders—including enlarged heart, heart failure, severely altered heart rhythm, and heart attack—that often lead to severe disability and death. Experts have long believed a drug combination would work better, but the safety and efficacy of the combination have not yet been proven.

GHIT’s grant will enable DNDi and Eisai to develop a combination therapy consisting of benznidazole and an experimental triazole compound known as E1224. Over the next two years, under the leadership of Dr. Isabela Ribeiro of DNDi, the collaborators will conduct a Phase II proof-of-concept study of the efficacy and safety of the combination. They will use data from this trial to help shape a Phase III multi-country study. The group will also work toward the registration of E1224, including several required chemistry, manufacturing and controls activities and nonclinical tests.

Pediatric Formulation of Gold Standard Drug for Schistosomiasis

A second GHIT grant awards US$1.86 million to a partnership involving Top Institute Pharma of the Netherlands, Merck KGaA of Germany, Astellas Pharma Inc. of Japan and Swiss Tropical and Public Health Institute. The award will enable the development and registration of a pediatric formulation of praziquantel, the gold standard treatment for schistosomiasis.

The disease, also known as bilharzia, is caused by parasitic worms that live in certain types of freshwater snails. Spread through contaminated freshwater, without treatment, chronic infection with schistosomiasis can cause an enlarged liver, blood in the stool and urine, and can even lead to an increased risk of bladder cancer. It’s endemic in 78 countries and affects more than 230 million people, including 100 million children—making it second only to malaria in terms of impact of a parasitic disease.

Praziquantel is currently recommended only for adults and children over the age of six; the partnership aims to create a formulation suitable for babies and young children. Proper treatment of these younger children with schistosomiasis is hampered due to missing clinical data and the fact that they cannot swallow these tablets because of their size and bitter taste. The partnership, which is supported by many of the world's leading schistosomiasis experts, has produced test batches of two new formulations, called racemate praziquantel and levo-praziquantel. Both formulations will be tested first in adults, with taste tests for children to follow. The funding will also help the partnership prepare for Phase II studies with the new formulation that will be selected for further development.

New Drug Compounds Against Wolbachia Bacteria

The final grant, for US$1.09 million, is awarded to the Liverpool School of Tropical Medicine and the University of Liverpool's collaboration with Eisai to investigate new drug compounds against Wolbachia bacteria. These bacteria work in concert with many parasitic roundworms, or filaria, and thus play a role in parasitic diseases like elephantiasis and river blindness (onchocerciasis), which together afflict more than 150 million people. Anti-Wolbachia therapy using the antibiotic doxycycline has proven safer and more effective than existing anti-filarial drugs in field trials held in recent years. However, the doxycycline requires 4-6 weeks of daily treatment course, and it is potentially harmful for young children and pregnant women. These barriers highlight the need for the development of new drugs targeted specifically against Wolbachia.

To date, the screening of more than 10,000 potential anti-Wolbachia compounds has revealed about 50 potential targets, leading to identification of about six types of molecules with anti-infective potential. Researchers will focus on two of these proposed chemical groups. The grantees plan a 12-month, head-to-head comparison of the two leading chemical types, with the goal of identifying a single candidate for potential drug development within one to two years.

Substantial Funding Boost for a Novel Vaccine Candidate for Tuberculosis

Today, GHIT also announced additional funding of US$5.65 million for work on a novel vaccine candidate to combat tuberculosis that is being co-developed by the National Institute of Biomedical Innovation, Japan’s Create Vaccine Co., Ltd. and Aeras, an international non-profit biotech based in Washington, DC. GHIT provided the partnership an initial grant of US$700,000 for this work in November, 2013. The additional funding will allow for further pre-clinical development to advance to a Phase I clinical trial to test its safety and immunogenicity. The vaccine candidate is focused on enhancing mucosal immunity to act as the first line of resistance against infection with tuberculosis, the first to target the patient's mucous membranes to keep TB from making an entry into the lungs. In mice, the vaccine increased the level of protection conferred by protection to BCG (Bacillus Calmette–Guérin) alone, the current vaccine against tuberculosis. BCG was invented nearly 90 years ago and provides insufficient protection to teenagers and adults, the group with the highest TB burden.

Moving “Hits” from Compound Libraries into Chemicals that Show Promise

The GHIT Fund's Hit-to-Lead Platform provides a budget of US$2.2 million over a period of two years with the goal of converting drug “hits” from the compound libraries of Japanese pharmaceutical companies into “lead compounds”—chemicals that show promise as anti-infectives but likely require further chemical modification before they can be tested as human drugs. This new program will help researchers find promising drug compounds that can fight deadly and debilitating infectious diseases.

“Japanese pharmaceutical companies and research institutes have considerable resources—including compound libraries that have yet to be screened to see what they might have to offer for infectious diseases like malaria, tuberculosis and neglected diseases,” said Dr. Kiyoshi Kurokawa, chair of the board of the GHIT Fund. “The Hit-to-Lead Platform will expand the drug pipeline for these diseases by bringing forward compounds that have not been previously screened or that are known to target mechanisms of action in a new and more effective way.”

The Hit-to-Lead Platform will essentially provide a bridge from early drug discovery into GHIT's typical grant phase, which begins with the optimization of these lead compounds.