Targeting diarrheal disease
An estimated 600,000 children under five years of age die every year from diarrheal disease, making it the second most common killer of young children after pneumonia. Survivors who are inadequately treated suffer long-term health problems. With about 2 billion cases of diarrheal disease globally every year, the world has an urgent need for safe, effective, and affordable treatments.
We are working to address the burden of cholera and other diarrheal diseases. In 2011, we received approval from the US Food and Drug Administration for phase 1 clinical trials of an investigational new drug called iOWH032 to treat acute secretory diarrhea resulting from diseases like cholera. This first-in-class synthetic drug is designed to be used in conjunction with oral rehydration therapy, providing faster relief of diarrhea symptoms and encouraging wider adoption of and compliance with the therapy. The drug candidate is currently in phase 2 trials in Bangladesh.
We continuously evaluate new treatment opportunities for infectious diarrheal disease and establish partnerships to move forward promising candidates for development. Currently, we are collaborating with Anacor Pharmaceuticals to find antibacterial compounds for treating bloody diarrhea (shigellosis) and with the Center for World Health and Medicine to identify potential anti-secretory drug candidates.
Ensuring the supply of malaria treatment
Malaria is a life-threatening disease transmitted by mosquitoes infected with parasites of the genus Plasmodium. Every year, malaria infects an estimated 216 million people, causing 655,000 deaths—most of them young children in sub-Saharan Africa. With proper surveillance and care, malaria can be prevented and treated.
Artemisinin-based combination therapy is the gold standard of malaria treatment. However, the supply of artemisinin derived from plants can be unstable, resulting in shortages and high cost of therapy.
To strengthen production of artemisinin, we set out to develop an innovative manufacturing process to create a non-seasonal, high-quality, and affordable supply of artemisinin.
We partnered with a diverse group of experts from the academic, biotech, and pharmaceutical sectors, and worked together toward a common goal—to use the latest technology and innovation to advance global health equity.
The project began in 2004, and our partners included synthetic biology innovator Amyris, Inc., the University of California, Berkeley, and the French pharmaceutical company Sanofi. The novel use of synthetic biology technology was based on pioneering inventions from UC Berkeley, Amyris, the National Research Council Canada Plant Biotechnology Institute, and GenoClipp Biotechnology BV. The chemistry expertise and the industrial experience and capacity of Sanofi helped bring this project from small laboratory experiments to production on the factory floor.
Over nine years, the partners took the idea developed in a lab to industrial-scale production of semisynthetic artemisinin. The entire manufacturing process takes approximately three months, less time than the botanical growing and harvesting cycle, and can be done in a controlled manufacturing setting to ensure high pharmaceutical consistency and quality.
In 2012, a substantial amount of semisynthetic artemisinin was produced and made available for testing by derivative manufacturers. Large-scale production of semisynthetic artemisinin launched in 2013, with a production goal of 35 tons, increasing to 50–60 tons in 2014, which corresponds to 80–150 million treatments for malaria.
Also in 2013, semisynthetic artemisinin achieved WHO prequalification. WHO’s decision means semisynthetic artemisinin has been evaluated and accepted for use in the manufacture of active pharmaceutical ingredients and finished pharmaceutical products. Prequalification creates a simplified process for manufacturers to obtain regulatory acceptance, possibly accelerating the availability of malaria treatments on the market.
Semisynthetic artemisinin will be produced at no profit, no loss, helping to keep the price at a fair market value. Providing the market with a second source of high-quality artemisinin will complement the current plant-derived supply, ensure a more stable flow of artemisinin to ACT manufacturers, and allow greater availability of treatments to patients.
New tool to stop the spread of HIV
PATH has entered into a new licensing agreement with pharmaceutical company Janssen R&D Ireland to develop an injectable form of the medicine rilpivirine that could provide a new tool in the fight to stop the spread of HIV.
The agreement paves the way for PATH and our partners to advance the product to phase 2 multisite safety studies in the United States and Africa, with trials anticipated to begin in 2014. The trials will build on the results of ongoing phase 1 work to establish the viability of the drug candidate. Our partners in this work include Janssen, the HIV Prevention Trials Network, and the Division of AIDS at the National Institutes of Health.