Drug Development Global Program

Advancing tools to fight soil-transmitted helminths

Nearly a quarter of the world’s population is infected with parasitic worms known as soil-transmitted helminths (STH), most commonly roundworm, whipworm, and hookworm.1 In impoverished communities, eggs from roundworm and whipworm and the larvae of hookworm enter the environment through the practice of open defecation. Limited sanitation and hygiene contribute to high rates of infection through hand-to-mouth contact, ingestion of contaminated food and water, or contact with bare feet. Globally, more than 880 million children are in need of treatment.

Once inside the body, STH may cause diarrhea, abdominal pain, general malaise and weakness, and chronic blood loss. Among children, infection can also be deadly. Moreover, STH infections contribute to and exacerbate anemia and malnutrition, conditions which put children at risk for long-term harm due to stunting and cognitive development deficiencies. Anemia also endangers the lives of pregnant women during pregnancy and birth.

Through mass drug administration with safe and effective anthelminthic drugs, the cycle of transmission from soil, to people, and back again can be stopped. Yet resistance to albendazole and mebendazole—the drugs currently used in mass drug administration campaigns—poses a significant risk, especially with repeated campaigns. Additionally, these drugs are contraindicated for women in their first trimester of pregnancy, leaving mother and fetus vulnerable to the effects of STH-induced anemia and malnutrition.

Our drug development efforts are aimed at developing new therapies, in addition to expanding access to existing treatment, in order to mitigate the threat of drug resistance and act as a complement to current treatment regimens for improved STH control.

Expanding access to tribendimidine

Tribendimidine (TrBD) is a widely studied anthelmintic drug supported by more than 20 years of clinical research and 10 years of approved use in China. Together with a consortium of government, nonprofit, and commercial partners, PATH intends to seek US Food and Drug Administration (FDA) approval for TrBD as a significantly improved treatment for hookworm infections. FDA approval is the initial step in a plan to incorporate TrBD in mass deworming campaigns in low-resource settings.

TrBD has demonstrated excellent efficacy against a variety of soil-transmitted helminth infections, and its unique mechanism of action, single-dose administration, and well-documented safety and efficacy make it an attractive next-generation therapy against STH, with the potential for enormous public health benefit.

To execute the project, PATH is leading a TrBD Consortium that includes the National Institute of Parasitic Diseases at the Chinese Center for Disease Control and Prevention, which is credited with the development of TrBD in China; TrBD manufacturer Shandong Xinhua Pharmaceutical Company; and Swiss Tropical and Public Health Institute.

This innovative collaboration—financed by Clarus, a leading life sciences investment firm, and the Global Health Investment Fund, an impact investment fund focused on neglected diseases and maternal/child health—is made possible by the FDA’s tropical disease priority review voucher (PRV) program. Any resulting PRV from a successful new drug application for TrBD with the FDA would be subsequently monetized, with the proceeds to be shared among investors, PATH, and TrBD Consortium partners. A portion of PRV proceeds will be set aside to make TrBD available in low-income countries, and financial returns will also support additional public health research and development efforts among consortium partners.

The TrBD Consortium is committed to ensuring that TrBD is successfully integrated into safe and effective mass drug administration programs and to this end, will pursue TrBD’s endorsement by the World Health Organization upon FDA approval and PRV monetization.

New hope for STH control: Cry5B

Cry5B is a powerful, naturally occurring anthelmintic protein from the soil bacterium Bacillus thuringiensis that holds considerable promise as a new therapeutic option for STH management. It has demonstrated efficacy in animal models, and its safety profile could permit use even in young children and in women in the first trimester of pregnancy. There is also evidence that resistance to the protein would develop more slowly compared to current treatments, potentially allowing for decades of intensive use.

PATH is leading a public-private partnership to accelerate the development of Cry5B with the aim of widening available treatment options for STH. Joining PATH in this effort are two Japanese companies—Meiji Seika Pharma Co., Ltd. and Ajinomoto Co., Inc.—and the University of Massachusetts Medical School.

Supported by investment from the Global Health Innovative Technology Fund, the partnership’s efforts currently focus on:

  • Development of appropriate microbial strains to express Cry5B.
  • Development of appropriate fermentation processes for growing Cry5B-expressing strains.
  • Research of needed processes for the purification of Cry5B from the production strains.

The combination of a Cry5B-based product with other existing anthelmintic drugs could further improve treatment effectiveness, broaden the types of infections that STH drugs can treat, and protect against resistance. Further, they could better enable the expansion of anthelminthic mass drug administration campaigns, reducing the global burden of STH.

1. World Health Organization (WHO). Soil-transmitted helminth infections. Fact Sheet. Geneva: WHO; 2016. Available at: http://www.who.int/mediacentre/factsheets/fs366/en/. Accessed December 8, 2016.