The excitement about TMC207 is tempered by the concern that despite the drug's promise, the pathway for worldwide regulatory approval is likely to be challenging. Depending on how quickly countries adapt their regulatory, diagnostic, and MDR-TB treatment programs, TMC207 may take years to roll out and become widely available to those living in high-burden, resource-limited settings. No TB drug has ever been made available through an expanded access program, making TMC207 a test case for how to ensure that a promising drug is made available as quickly as possible to those with limited or no treatment while making sure that it is used appropriately. There are lessons to be learned from HIV drug development about providing experimental drugs through expanded access.
But TB poses different challenges because pharmaceutical companies believe the target market to be small and poor. In most countries TB is treated with a public health approach that prioritizes the public good over individual patient needs. In the 1990s, during the highly active antiretroviral therapy (HAART) revolution, pharmaceutical companies took on the responsibility of providing expanded access to patients in need because it helped to generate pre-regulatory demand for the drug and taught health care providers -- many of them private -- how to use the drug. Because TB is a disease of the poor, many believe that there is limited potential for pharmaceutical companies to make substantial profits and that therefore they are less willing to bear the full cost and responsibility for expanded access programs -- let alone the full costs of scaling up high-quality MDR-TB diagnosis, treatment, and supportive care.
There is also concern that if TMC207 is used inappropriately -- with too few effective background drugs -- new TB-resistant strains could rapidly emerge, thus limiting the drug's long-term impact on the TB pandemic.
Acknowledging these programmatic challenges and the urgent need and moral imperative to ensure access to promising TB drugs to people who are dying, TAG and others have been grappling with questions of how best to target the expanded access program for TMC207 in order to reach the individuals in greatest clinical need and to ensure that they receive care in high-quality programs without imposing unnecessary restrictions that would limit access. At the same time steps must be taken to ensure that the drug is given with appropriate active background TB therapy in the context of regular diagnostic and drug susceptibility testing to limit and monitor the emergence of drug resistance. TMC207 is farthest along in its development, so all eyes have been on Tibotec -- it is encouraging that the company has taken the initiative to develop a plan for providing preapproval access to the compound. While in Berlin for the World Lung Conference, TAG met with Tibotec to review the company's draft plan for an expanded access program and provided feedback on how to broaden its scope and make it easier for well-functioning programs to provide the compound to their patients.
Poor cure rates for drug-resistant TB and the limited understanding of how best to use current drugs make the need to establish an expanded access program for new treatments for drug-resistant TB more acute than for drug-susceptible TB, and developers of these new drugs need to be prepared. Otsuka's OPC-67683 is not far behind TMC207 in its development, thus Otsuka also needs to start planning for how it will roll out an expanded access program. TAG is working with researchers, providers, and activists to develop guidance on the type of mechanism that should be in place until the drugs are available to the general public; a document is expected to be completed in early 2011 and will include what worked in providing expanded access to antiretroviral drugs but will focus on addressing the specific challenges facing TB patients, health care providers, and national TB programs in accessing experimental treatments.
There are only a few persons left working in TB who can remember the discovery of the last class of drugs, so after many years of so little, the promise of TMC207 and the current activity in TB treatment research has generated an uncommon feeling of excitement in the field. The ability to drastically improve treatment outcomes for people with drug-resistant TB and make treatment for drug-susceptible disease easier to complete finally feels within reach.
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