TB Alliance launches first clinical trial of a novel TB drug regimen

This Phase II trial, called NC001 or New Combination 1, tests the new TB drug candidates PA-824 and moxifloxacin in combination with pyrazinamide, an existing antibiotic commonly used in TB treatment today. Based on pre-clinical data, the combination shows potential to shorten treatment time for virtually all tuberculosis patients and harmonise the treatment of DS-TB and MDR-TB treatment with a single three-drug regimen. This is a particularly significant advance for MDR-TB patients, who today must take multiple types of drugs, including injectables, daily for up to two years. If successful, the experimental regimen will offer a shorter, simpler, safer, and more affordable treatment option for MDR-TB, an emerging global health threat. Both new compounds are being developed by the non-profit organisation TB Alliance, one (moxifloxacin) in partnership with Bayer HealthCare AG.

More than just new drugs required

"We need more than a new drug to eradicate TB - we need entirely new regimens of TB drugs," said Mel Spigelman, M.D., President and Chief Executive Officer, TB Alliance. "The potential to offer a single regimen to treat both drug-sensitive and multi drug-resistant TB represents a monumental advance in the treatment of patients worldwide, and a tremendous step toward simplifying the delivery of TB treatment globally."

Treating active TB requires a combination of drugs to prevent the development of drug resistance. Traditionally, researchers tested one new drug at a time in a series of lengthy and expensive clinical trials, meaning it would take decades to develop a completely novel drug combination. This new approach to drug development enables combinations of previously unregistered TB drugs to be tested together, with the goal of introducing truly innovative regimens in only a fraction of that time.

The trial

This research approach is being championed by the Critical Path to TB Drug Regimens, an initiative established to tackle the regulatory and other challenges associated with TB drug development. CPTR was founded in March 2010 by the Bill & Melinda Gates Foundation, the Critical Path Institute, and the TB Alliance. Nearly a dozen pharmaceutical companies, civil society organisations, the European and Developing Countries Clinical Trials Partnership (EDCTP), and others have signed on to the initiative's guiding principles. The US Food and Drug Administration, other regulatory bodies, and the World Health Organisation have all shown support for this initiative.

The trial involves 68 participants at two centres in South Africa, each receiving two weeks of treatment and three months of follow-up to evaluate effectiveness, safety, and tolerability. NC001 is an early bactericidal activity trial and is supported financially by United States Agency for International Development, the Bill & Melinda Gates Foundation, and the United Kingdom's Department for International Development.

A desperate need

There is a desperate need for new and better TB treatments to address today's growing pandemic, which kills nearly 2 million people each year. There have been no new TB drugs for nearly 50 years and, until the past decade, no pipeline of TB drug candidates. Now, with increased investments in TB R&D, there are 9 promising TB compounds in the pipeline from six antibiotic classes, making combination testing of new TB drugs possible.

"New and powerful drugs to combat TB and MDR-TB are essential to achieving TB control goals outlined in the Global Plan to Stop TB 2011-2015 and ultimately to eliminate TB," said Mario Raviglione, M.D., director of the World Health Organisation's Stop TB Department. "It is extremely encouraging to see a growing pipeline of TB drug candidates that may revolutionise TB care and committed sponsors moving with speed and efficiency towards new regimens."

NC001 also tests additional two-drug combinations (TMC207/pyrazinamide and PA-824/pyrazinamide) that may prove to be the building blocks of future regimens. Regimen development may become the new gold standard in TB research and offer lessons for other diseases requiring combination treatment, such as cancer, hepatitis C, and malaria. However, there remains a vital need for funding to bring new TB regimens through late-stage clinical trials.

"We desperately need more funding and creative approaches to impact the global pandemic," reported Joanne Carter, Executive Director, RESULTS Educational Fund. "Support for research and development of new TB regimens is critical to reducing the impact of this disease and helping to eliminate one of the major health causes of entrenched poverty."

About the Global Alliance for TB Drug Development

The TB Alliance is a not-for-profit organisation dedicated to finding faster-acting and affordable drug regimens to fight tuberculosis. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. The TB Alliance operates with funding from the Bill & Melinda Gates Foundation, the Netherlands Ministry of Foreign Affairs, the United Kingdom Department for International Development, the United States Agency for International Development, and the United States Food and Drug Administration. For more information please visit tballiance.org

About tuberculosis:

TB kills nearly 2 million people each year--1 person every 20 seconds. It is the third leading cause of death of women of child-bearing age in the developing world and the leading killer of people with HIV/AIDS. Due to the length and complexity of the current TB treatment, many patients are unable to complete their treatment, leading to increasing drug resistance, an emerging global health threat. More than half a million cases of drug-resistant TB emerge yearly. Unless these trends are reversed, drug resistance raises the spectre of future, untreatable TB epidemics.