The TB Pandemic
Tuberculosis is a bacterial infection that is spread from person to person primarily by breathing infected air during close contact. TB kills someone approximately every 20 seconds — 3,800 people every day, or 1.3 million in 2012 alone, according to the latest estimates from the World Health Organization (WHO). TB is second only to HIV as the leading infectious killer of adults worldwide, is the third largest killer of women in their reproductive years, and the leading infectious cause of death among people with HIV/AIDS.
In recent years, the world has seen a rapidly emerging epidemic of drug-resistant TB (MDR-TB or multi drug-resistant and XDR-TB or extremely drug-resistant TB), which is highly lethal and extremely expensive and complicated to treat. Because the treatment regimen for TB is long and complex, many patients are unable to complete the course of treatment, enabling their disease to develop drug-resistance. Once a drug-resistant strain has developed, it can be transmitted directly to others.
The current first-line TB drug regimen of four drugs is nearly 50 years old, takes six to nine months to complete and has significant side effects. All too often, these drawbacks cause patients to default on their treatment and, consequently, resistance to TB drugs is spreading in every corner of the world. Treatment for MDR-TB or XDR-TB can last 2 years of longer, consists of many drugs, including injectibles, many of which have significant side effects and is extremely expensive and resource-intensive to deliver.
There are an estimated 450,000 cases of MDR-TB and XDR-TB around the world each year. With the rapid and lethal spread of drug-resistant TB, speeding the development of new, simpler and more effective drug regimens is no longer just an option, but a major public health imperative.
Tuberculosis must be treated with drug regimens to prevent the development of drug-resistance. However, to test promising combinations together, there must be a sea change to traditional thinking about TB research—and the change must be adopted by everyone: drug sponsors, global regulators, WHO, patients, and other stakeholders throughout the TB landscape.
The Impact of New TB Regimens
Novel treatment regimens would drastically shorten and simplify the treatment of both drug-sensitive and drug-resistant tuberculosis, and enable both forms of the disease to be treated with the same multidrug treatment. However, using the traditional model of TB drug development, it could take decades to develop such a regimen.
Treating active TB requires a combination of multiple drugs to prevent the development of drug resistance. In the past, individual TB drug candidates were developed and registered separately, by being substituted (or added) one at a time the existing standard, four-drug, combination TB therapy. Because each substitution (or addition) could take six years or longer, the approval of a new four-drug TB regimen, through successive trials, could take nearly a quarter of a century to develop under this framework. With millions dying of TB each year, the world cannot wait that long for the tools needed to stop this devastating disease.
Instead, CPTR supports a new paradigm to speed promising TB treatments to patients. It focuses on shifting the unit of development from an individual drug to combinations of drugs, which can be tested together and developed as a regimen from early clinical testing. Advances in regulatory science will help clearly evaluate experimental TB drugs both on their own and within the context of a regimen. This new approach has the potential to shorten the time needed to develop new TB treatment regimens by decades, as well as significantly reduce development costs.
In 2012, the first combination trial of a new TB regimen was completed successfully. TB Alliance reported positive findings in the NC-001 trial, which tested the “PaMZ” regimen that contained multiple new TB drug candidates. Since then, additional trials of PaMZ and other new regimens have been completed, and the world is closer than ever to novel TB treatment regimens.