Of the estimated 10.4 million new tuberculosis cases globally in 2015, nearly 0.5 million were multi-drug-resistant (MDR). Another one million were resistant to rifampicin drug alone. India accounted for 2.84 million new cases in 2015, of which 79,000 had MDR TB. There were 1.4 million TB deaths worldwide in 2015.
For the first time in nearly 50 years, two new drugs, bedaquiline and delamanid, were approved by the U.S. Food and Drug Administration for MDR-TB cases. The accelerated approval of bedaquiline was based on interim Phase IIa data.
Lack of data
The lack of large-scale safety data and the paucity of effective TB drugs, especially for MDR-TB, are the reasons for the World Health Organization (WHO) to insist that the drug be used only when all “options to treat TB using the existing drugs have been exhausted.”
The WHO also makes it abundantly clear that all efforts should be made to avoid TB bacterium from developing resistance to bedaquiline as a result of misuse.
Despite the gravity of the situation and a near-empty drug chest to fight TB in India, a WHO list, released on February 27, of drug-resistant bacteria that pose the “greatest threat to human health” and for which new drugs are desperately needed, has no mention of Mycobacterium tuberculosis, the bacterium that causes TB.
Not a priority pathogen?
This is the first time that the WHO has released such a list and the prime objective of listing the “priority pathogens,” in its own words, is to “guide and promote research and development of new antibiotics… and to address the growing global resistance to antimicrobial medicines.”
The list is divided into three categories — critical, high and medium — based on the urgency of need for new drugs. While the WHO reasons that malaria and HIV have not been included in the list as they are not bacterial infections, it cites a different reason for not including TB bacteria. According to the WHO, TB bacterium was not included in the list as it is already targeted by other “dedicated programmes.”
In a strongly worded open letter to WHO director-general Margaret Chan, The Union Against Tuberculosis and Lung Diseases, or simply The Union, says it is “outrageous” that Mycobacterium tuberculosis was not considered for inclusion as it is “already a globally established priority for which innovative new treatments are urgently needed.” “This explanation defies reason [and] contradicts the stated intent of the global priority pathogens list’s methodology to define the list,” the letter reads. “TB’s exclusion sends the false and counterproductive message that drug-resistant TB is not an urgent public health threat,” the letter says. It also sends a strong message to policy-makers to “de-prioritise TB research,” it adds.
Meets criteria for inclusion
The reason why The Union has reacted so strongly is that the TB bacterium meets each of the 10 criteria used for inclusion in the list — how deadly the infections are, the number of infected people in a community, prevalence of resistance, how easily the bacterium spreads from one person to another, options to prevent the infection in hospital and community, treatment options and whether new drugs are already in the R&D pipeline.
The WHO states that new antibiotics most urgently needed will never be developed in time if it is left to market forces alone. This is best demonstrated in the case of TB. It took nearly 50 years for new TB drugs to be approved for MDR-TB and not a single antibiotic has been developed for drug-sensitive TB in half-a-century.
Since the WHO has stated that the list has been developed to allow periodic revisions and inclusions of other pathogens, including viruses and parasites, The Union wants the TB bacterium to be included in the list before the WHO publishes the full protocol and results by the end of May 2017.