Also in this issue

Starting Up
• Battling Tobacco Use in Southeast Asia
• Where Is the Money? A Snapshot of Education Financing in El Salvador
• Community-Based Water Sector Management: Is It Really Working?

Publications
Brinkerhoff, "Rebuilding Governance in Failed States and Post-Conflict Societies: Core Concepts and Cross-Cutting Themes."
Brinkerhoff, "Accountability and Good Governance: Concepts and Issues."
Crouch, "El Sector Educación: Estándares, Rendición de Cuentas y Apoyo."

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A Possible Breakthrough in TB Drug Development

Tuberculosis (TB) is one of the leading killers worldwide. Nearly one-third of the world’s population is infected with latent TB, and even though only 10 percent of those infected are likely to become sick, the disease still kills one person every 15 seconds—the equivalent of 2 million people a year.

Increasingly resistant to traditional treatment, the disease is spreading rapidly in some developing countries, which often lack affordable medications, adequate health care systems, and the diagnostic tools necessary to recognize the disease in its early stages and prevent its spread. The current treatment for TB infection, which has been used for more than 40 years, is long and cumbersome. A typical regimen lasts 6 months, involves four separate drugs, and includes an 8-week period of taking up to 22 pills a day. Poor compliance with this complex drug regimen contributes to the development of drug-resistant strains of TB that no longer respond to standard treatment. Indeed, to enforce compliance and help stem the emergence of resistant strains, patients can be jailed for refusing to adhere to treatment in many countries, including the United States.

Working with the TB Alliance, RTI is managing the development of a promising new anti-TB drug, PA-824, which entered human trials in June 2005. PA-824 has the potential to shorten the current 6-month treatment regimen, which was developed more than 40 years ago. [PHOTO: MDS Pharma Services]

Working with the Global Alliance for TB Drug Development (TB Alliance), RTI is managing the development of a promising new treatment. With funding from the U.S. National Institute of Allergy and Infectious Diseases (NIAID), RTI began searching for possible treatments in 1999. Seven years later, the search has paid off. PA-824, one of a class of compounds known as nitroimidazoles, entered human trials in June 2005.

According to Dr. Doris Rouse, director of IDG’s Global Health Technologies, the anti-TB drug has the potential to reduce treatment time from 6 to 3-4 months. Because much of the cost of current TB treatment comes from treatment monitoring—most patients are required to go to a health clinic daily so their compliance with the drug regimen can be monitored—shorter treatment duration will significantly reduce the cost of treatment and likely improve patient compliance. In laboratory tests, PA-824 also has been effective against resistant TB strains.

Public-Private Partnership

This breakthrough drug is unique not only because of its health benefits, but also because it has been developed through a public-private partnership. In 2000, recognizing the need for innovative approaches to developing anti-TB drugs, representatives from academia, industry, major agencies, nongovernmental organizations, and donors—including RTI—met in Capetown, South Africa, and called for the creation of the TB Alliance. As a nonprofit public-private partnership, the TB Alliance is devoted to developing new drugs to treat TB and making them accessible to those who need them. RTI remains a member of the TB Alliance Stakeholder Association. RTI’s activities in support of the TB Alliance include preparing epidemiology and market assessments; and partnering with pharmaceutical companies, research labs, foundations, and international organizations to cooperatively develop, test, and introduce new TB therapies. RTI led a global collaboration of public and private sector organizations to prepare a report on the Economics of TB Drug Development; this comprehensive report examines the epidemiology of TB, potential markets for new TB drugs, cost of creating new TB drugs, and options for funding and conducting drug development.

In its role under the initial NIAID contract, RTI was charged with accelerating the commercial availability of TB treatments developed by universities or pharmaceutical companies. To do this, Rouse’s team began a worldwide search for promising drugs. One such drug, PA-824, had been developed by researchers at PathoGenesis (acquired by Chiron in 2000). In 2002, Chiron licensed PA-824 to the newly formed TB Alliance, agreeing that the TB Alliance would not pay royalties on sales of the drug in developing countries. Chiron would, however, have an option to market the drug in the United States and Europe should the drug be approved in those countries. This groundbreaking deal will enable the TB Alliance to distribute the drug to developing countries at the lowest cost possible.

A district health team nurse visits the house of an elderly female TB patient in Samoa. Today, TB infects more people in the world than at any other time in history and is the leading killer of HIV-infected people. [PHOTO: Andy Crump (1999), WHO/TDR/Crump]

Serving as the project manager for PA-824 for the TB Alliance, RTI’s team is shepherding the drug through the regulatory approval process. The TB Alliance, through Rouse’s team, has thus far contracted and collaborated with 26 organizations in nine countries to reach the present stage of development. After 2½ years of research and development and preclinical studies, Rouse’s team submitted, on behalf of the TB Alliance, an investigational new drug application to the U.S. Food and Drug Administration in March 2005 and the TB Alliance was approved to start clinical trials in June—the first time an anti-TB drug developed by a nonprofit has entered clinical trials. Following successful single-dose studies in humans, PA-824 entered multidose studies in the Phase I trials in November 2005.

“The start of Phase I clinical trials offers a bright spot on the long road to providing shorter and more effective TB treatments,” Rouse said. If trials continue to show that the drug works and is safe, it could be approved as a new drug by 2011. Although that is a long way off, it’s remarkable because the TB Alliance has been able to shepherd the drug through the long process as rapidly as standard pharmaceutical company timelines. “The public-private partnership is an important option for creating new drugs to treat diseases of developing countries,” Rouse said. “The TB Alliance’s work has shown that it’s an effective option for developing promising new drugs and ensuring affordable access in countries with limited resources.”

More Information:
Doris Rouse, e-mail rouse@rti.org