TB Alliance Advances Two Drugs In Clinical Trials On Path To Faster, Better Tuberculosis Treatments

Trailblazing Phase III Trial Seeks to Shorten TB Treatment; Novel Candidate in Phase II Offers Hope for More Effective, Simpler Cure

November 7, 2007

NEW YORK & CAPE TOWN, South Africa--The Global Alliance for TB Drug Development (TB Alliance), a not-for-profit, product development partnership accelerating the discovery and development of new drugs to fight tuberculosis (TB), today announced the advancement of two promising TB treatment candidates into the next phases of research in patients, marking pivotal milestones in the development of faster, simpler regimens.

Moxifloxacin - Phase III

A large scale, pivotal Phase III clinical trial in TB patients is beginning with the antibiotic moxifloxacin, already approved for other respiratory indications. The study - launching initially at six clinical trial sites in Africa - is designed to test whether a four-drug combination regimen including moxifloxacin can reduce treatment time for TB. Earlier studies suggest that combination therapy including moxifloxacin has the potential to shorten the treatment period for drug-susceptible TB from at least six months to four months or less.

PA-824 - Phase II

PA-824 is the first novel TB drug candidate developed by a not-for-profit organization to reach clinical trials, and is now in its first test in TB patients in Cape Town. Due to its novel mechanism of action, PA-824 shows promise for treatment of drug-susceptible and drug-resistant TB, and may contribute to treatment shortening when in an effective combination regimen.

"Two new promising TB drugs in our portfolio are moving forward in clinical trials, offering patients worldwide the hope of a markedly shorter and better TB treatment," said Dr. Maria C. Freire, CEO and President of the TB Alliance. "This is a historic milestone in our accelerated drive to develop new TB drugs that fight the disease in different, faster and better ways to help save millions of lives."

A shorter TB regimen, which could be possible with new drugs such as moxifloxacin and PA-824, should lead to improved patient compliance, helping to maximize cure and limit the emergence of new, resistant strains. Novel compounds like PA-824, which fight TB in different and potentially better ways, are needed to battle the growing threat of drug-resistance.

The moxifloxacin Phase III program, called REMoxTB, is being led by investigators from UCL (University College London) and the British Medical Research Council, and is the pivotal next step in a groundbreaking TB development program between the TB Alliance and Bayer HealthCare AG (Bayer), which developed and markets moxifloxacin globally for other indications. Recruitment for the global REMoxTB program will begin at six sites in Kenya, South Africa, Tanzania and Zambia.

The study will assess whether each of two, four-month regimens substituting moxifloxacin for one of the current standard drugs (ethambutol or isoniazid) is equally effective as the standard six-month therapy in terms of failure and relapse. Phase III studies are needed to build on results of three shorter, smaller Phase II studies, which used similar substitution strategies with moxifloxacin.

In the other key TB Alliance clinical advance, PA-824 is undergoing a Phase IIa Early Bactericidal Activity (EBA) study in TB patients, an evaluation of its short-term potency given as a single drug. Patients enrolled at two sites in Cape Town receive either PA-824 or the standard, four-drug TB treatment for 14 days. If Phase IIa EBA results are positive, the drug will advance to Phase IIb studies in which PA-824 will be given in combination with other current, effective drugs to further test its safety, tolerability and efficacy. Phase I studies of PA-824 in healthy volunteers revealed that the drug is well-tolerated with no dose-limiting adverse events.

"Our clinical program highlights the importance of rigorous standardization in research methods that should serve as a solid foundation for future TB drug development," said Dr. Mel Spigelman, TB Alliance Director of Research and Development. "With these clinical advances, and our growing TB drug pipeline, we are confident we will succeed in developing new, novel regimens that are faster-acting, work against drug-resistant disease, and help improve treatment of the growing number of patients co-infected with TB and HIV."

About Moxifloxacin

Moxifloxacin is a member of the fluoroquinolone class of antibiotics. It has already been approved for other indications, including acute respiratory infections, and is the first drug in the TB Alliance portfolio to enter a pivotal registration trial. Moxifloxacin has a different mechanism of action from those of current first-line TB drugs and has demonstrated activity against Mycobacterium tuberculosis (M.tb), the bacillus that causes TB, in both in vitro and in vivo studies. Unlike some existing TB drugs, moxifloxacin does not interact with enzymes that are involved in the body's handling of antiretroviral therapies used to treat HIV patients.

Moxifloxacin has an excellent safety record, having been used in more than 76 million patients in more than 140 countries. If clinical development is successful, the TB Alliance and Bayer are committed to making moxifloxacin affordable and available for TB patients where it is needed most, especially in developing regions.

About PA-824

PA-824 is a member of the nitroimidazole class. The TB Alliance received worldwide exclusive rights to PA-824 and its analogs for the treatment of TB in a landmark 2002 agreement with Chiron, now part of Novartis, which includes ensuring that the technology will be made available royalty-free in endemic countries.

The U.S. Food and Drug Administration (FDA) recently approved a request for orphan drug designation for PA-824. The Orphan Drug Act is designed to reduce the costs of developing and registering drugs for some diseases and conditions that are rare in the U.S. The designation confers a number of benefits for the development of PA-824, including a waiver of the nearly $1 million fee usually paid on submission of a New Drug Application. The European Union has just approved similar Orphan Medical Product status for PA-824. The FDA also has granted PA-824 fast-track designation, which is designed to expedite the application and review process for products that have the potential to address a serious or life-threatening condition.

About TB Disease

Tuberculosis (TB) kills someone every 20 seconds -more than 1.5 million each year, according to the World Health Organization (WHO).

The WHO estimates about one-third of the world's population is infected with Mycobacterium tuberculosis (M.tb), the bacillus that causes TB, and the disease is second only to HIV as the leading infectious killer of adults worldwide.

New drugs are critical to ending the needless burden of TB. The current four-drug TB regimen, a product of the best scientific advances of the 1960s, works for drug-susceptible TB - as long as patients complete at least six months of treatment. The problem is, many do not or cannot. As patients start to feel better within a few weeks, many find it difficult to complete the cumbersome treatment or maintain access to the drugs. This can lead to the emergence of TB strains that are resistant to first-line - and even second-line - drugs.

Reducing the time it takes for patients to finish the full course of drugs needed for a cure would make treatment much easier for patients and healthcare workers, saving lives and money, and curbing the threat of deadly drug-resistance.

About The Global Alliance for TB Drug Development

The Global Alliance for TB Drug Development (TB Alliance) is a not-for-profit, product development partnership accelerating the discovery and development of new TB drugs that will shorten treatment, be effective against susceptible and resistant strains, be compatible with antiretroviral therapies for those HIV-TB patients currently on such therapies, and improve treatment of latent infection.

Working with public and private partners worldwide, the TB Alliance is leading the development of the most comprehensive portfolio of TB drug candidates in history, and is committed to ensuring that approved new regimens are affordable, adopted and available to those who need them.

The TB Alliance operates with funding from the Bill & Melinda Gates Foundation, the Rockefeller Foundation, Irish Aid, the Netherlands Ministry of Foreign Affairs (DGIS), the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID). For more information on TB drug development and the TB Alliance, please visit http://www.tballiance.org/

Support for the TB Alliance clinical development of moxifloxacin and PA-824 comes from the Bill & Melinda Gates Foundation and USAID. In addition, direct funding to UCL for the REMoxTB trial was supplied by the European and Developing Countries Clinical Trials Partnership (EDCTP).