The Global Alliance for TB Drug Development (TB Alliance) is a non-profit organization dedicated to the discovery and development of new, faster-acting and affordable tuberculosis medicines.
The TB Alliance expects to register a new anti-TB regimen that could cut the duration of tuberculosis treatment one-third by 2013. In the long-term, the TB Alliance’s goal is to develop a drug regimen that will reduce TB treatment to 10 doses from 130; be effective against drug resistant strains of TB; work with the antiretroviral drugs used to treat HIV; and improve the treatment of latent TB infection.
Tuberculosis infects one third of the world’s population, kills two million people each year, and costs the global economy $16 billion annually. However, research and development for new TB drugs came to a virtual standstill after the 1960s. Today, a four drug combination therapy exists, but it takes six months or more to be effective. This requires a degree of monitoring (See Direct Observational Therapy, Shortcourse) beyond the capacity of the health infrastructure in many countries; adequate TB treatment is available to less than half of the most infectious cases. This can inhibit control of the disease and fuel the rise of drug resistance. TB is also the number one killer of AIDS patients, but it is generally agreed that current TB treatments do not work well with the antiretroviral drugs used to treat HIV.
The TB drug market lacks sufficient financial incentives to stimulate a single private pharmaceutical company to invest in the new research required to sustain a treatment pipeline. The TB epidemic is concentrated in developing countries where drugs must be low in cost to remain accessible. It does not generate the kind of revenue streams that private companies usually deem necessary to justify the research costs and strategic risks involved in pharmaceuticals. The TB Alliance was designed to be the primary instrument to fill this vacuum and to ensure that new anti-TB drugs are affordable and accessible in endemic countries.
The TB Alliance was conceived at a February 2000 meeting in Cape Town, South Africa, where 120 representatives from academia, industry, major government agencies, non-governmental organizations and donors gathered to discuss the problems of tuberculosis treatment. Participants stressed the need for faster-acting, novel TB drugs and highlighted the scientific opportunities involved. The resulting "Declaration of Cape Town" provided a road map for TB drug development and outlined the need for creation of the TB Alliance. Maria Freire was appointed as the first Chief Executive Officer and President in 2001 and served in that capacity until 2008, when she left the TB Alliance to become President of the Albert and Mary Lasker Foundation. The current CEO and President is Melvin Spigelman.
The TB Alliance is a non-profit public-private partnership. It operates like a virtual biotechnology firm, collaborating with research institutions and pharmaceutical companies so that risks and incentives are shared. While retaining management oversight of its drug development projects, the TB Alliance out-sources the development of potential drugs to public and private partners, providing funding and scientific guidance. Depending on the project, the TB Alliance either co-invests and co-develops a project, funds and manages it directly, or in-licenses the technology or intellectual property involved. Project diversity is a stated goal, with potentials compounds selected from a variety of chemical classes, with a wide range of targets within the TB organism, Mycobacterium tuberculosis.
As of January, 2009, the TB Alliance has 16 drug projects underway, either in either discovery or clinical or phase. Part of the TB Alliance’s stated mission is to ensure that any new treatments are affordable and accessible in the developing world, and that they are adopted as soon as they become available. Pricing terms are included in all licensing contracts and end products are designed to be easy to take. The TB Alliance also collaborates with national and international partners, working to ensure that new therapies are adopted and accessible to healthcare providers and patients via local channels.
Adverse Effects and Patient Compliance
Some anti-tuberculosis agents are known to have some side effects, which limits their use for mono-therapies only. This poses a limitation for their use in combination therapy, for overcoming drug resistance. Also, some of the side effects may lead to a low level of compliance by the patient, i.e. not completing the full course of treatment. This creates conditions within the patient that enable drug resistance to arise or even to become prevalent. In view of such situations it is often recommended that novel anti-tuberculosis agents need to be discovered and developed.
Drug resistance occurs for several reasons, often as a natural consequence of gene mutations and selection, as a consequence of drug-efflux mechanisms, or due to drug modifying enzymes. Under conditions of medical treatment, mutants that are resistant to the drug may escape the drug's action, survive and multiply further. This is one of the reasons why combination therapies are often essential for treating tuberculosis infections and most infectious diseases. At the present time, three of even four tuberculosis drugs are given as a combination therapy, over an extended period of time, though patient compliance and side effects continue to be a medical issue. Some strains of the tuberculosis pathogen are resistant to all three or four tuberculosis drugs. In view of the contagious nature of tuberculosis, especially among persons with weak immunity, drug resistance is considered to be a serious public health issue.
Investigational New Drugs
Investigational new drugs (IND) are clinical candidates that are safe and efficacious in the animal models of infection. Usually, these are new chemical entities (NCE) with a novel mechanism of action. Investigational new drugs have to be approved by the national or international medical regulatory authorities, for clinical testing and development in humans. IND's are usually discovered and developed to overcome the limitations of drugs that are or have been in clinical use.
The Pathogen Box
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Research & Development Centre
Research and Development Centres (R&D) for infectious diseases usually are staffed with scientists and physicians in the fields of biology, chemistry, physics, mathematics, pharmacology, veterinary science and medicine. Depending on the number of projects, it is a common practice for these research and development Centres to be staffed with about 150 scientists and physicians, with an organizational framework that is appropriate for pharmaceutical research and development.