Doctors Without Borders Funds TB Research Amid Controversy on WHO Priority Pathogens List

Tuberculosis (TB) has overtaken HIV as the world’s most fatal infections, resulting in the death of more than 1.8 million people in 2016 alone, according to Medecins Sans Frontieres.

Despite these chilling numbers, the World Health Organization (WHO) left the disease off its “Priority Pathogens” list. The first-ever list was published February 27^th and included “12 families of bacteria that pose the greatest threat to human health.” The decision to exclude TB from this list has generated a firestorm of controversy within the infectious disease and public health arenas.

In a statement released with the list, WHO officials noted that TB “was not included in the list because it is targeted by other, dedicated programs.” Having said that, the organization acknowledged that the infection’s “resistance to traditional treatment has been growing in recent years.”

Several organizations have responded publicly. In a Letter to the Editor of the Financial Times, for example, the Kaiser Family Foundation (KFF) wrote that WHO “has badly misstepped in leaving out Mycobacterium tuberculosis from its list of 12 priority superbugs for which new antibiotics are needed urgently… Although TB is a bacterial disease, currently available antibiotic medicines simply cannot keep up against rapidly evolving resistance… TB patients desperately need new and better medicines, and drug-resistant TB needs to be acknowledged as the biggest health threat in the antibiotic resistance crisis.”

The KFF letter goes on to describe the TB research community as “badly underfunded” and WHO’s decision as “baffling.” The group, along with several other advocacy and research organizations, including the Stop TB Partnership, the TB Alliance, and the International Union Against Tuberculosis and Lung Disease, has requested that WHO revisit the decision. However, in response to a query on the matter by Contagion^®, a WHO spokesperson said that there are no plans to add TB to the “priority pathogens” list, but that the organization “plans to consult further with stakeholders and users of the [publication] on the value of evaluating other groups of pathogens for R&D prioritization using the same process.” In fact, WHO believes there is “already consensus that tuberculosis is a top priority for R&D for new antibiotics.”

The spokesperson, Olivia Lawe Davies, added, “Communication of the reason to exclude TB has clearly been inadequate... WHO has recognized TB as a global R&D priority for many years, most recently through the Global Tuberculosis Report 2016, as well as the End TB Strategy, in which intensified R&D is one of the three pillars. The purpose of the priority pathogens list was to define research and development needs for bacteria not already identified as R&D priorities, for which there are not new products in the pipeline. The bacteria included in the list cause severe and often deadly infections, are resistant to multiple antibiotics, and R&D has been very limited. The analysis carried out to develop the [list] was similar to that used for the R&D Blueprint for Action to Prevent Epidemics priority list of pathogens for which there is an urgent need for vaccines and treatments. This Blueprint list also excluded diseases that are established R&D priorities, such as pandemic influenza. The non-inclusion of TB in the [the list] does not indicate that WHO believes TB is not an R&D priority.”

Meanwhile, the Treatment Action Group (TAG), an organization of healthcare activists focused on diseases such as HIV and TB, among others, reports that while the United States continues to lead global funding efforts for TB-related research, contributing nearly 40% of the $674 million in funds raised in 2014, government allocations have “flat-lined” since 2009, at roughly $250 million annually. TAG writes that “TB R&D is woefully underfunded, with a gap of $1.3 billion to meet the funding targets set by the Global Plan to Stop TB”—which, ironically, is a partnership between the Stop TB Partnership and WHO.

Several other NGOs—namely, Médecins Sans Frontières (MSF), Partners In Health, and Interactive Research & Development—have initiated a UNITAID-funded Phase III clinical trial designed to research novel approaches to treating Multidrug-Resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). The so-called “endTB” clinical trial is centered in Tblisi, Georgia and will focus on the safety and efficacy of bedaquiline (Sirturo, Janssen) and delamanid (Deltyba, Otsuka) in MDR-TB. The 2 drugs are the first novel treatments developed for TB in decades.

“While both drugs have shown very promising results when added to the standard, long and badly-tolerated MDR-TB treatments, we know little about how to optimize them,” Francis Varaine, MD, co-principal investigator of the endTB clinical trial and leader of MSF’s TB working group said in a statement released by the organization. “Without further research, we are only scratching the surface and patients continue to suffer.”

Of course, this suffering is due not only to the ravages of TB but also the side effects of many antibiotics used to treat it. The clinicians heading up the endTB trial hope to enroll 2,600 MDR-TB patients on treatment with the new TB drugs in 6 countries: Georgia, Kazakhstan, Kyrgyzstan, Lesotho, Peru, and South Africa. MSF was also involved in the launch of the TB PRACTECAL trial in Uzbekistan in January. The Phase III trial will assess the potential role of bedaquiline and pretomanid (PA-824), the latter of which was developed by biotech firm Pathogenesis Corp. and transferred to the TB Alliance.

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.