In the fight against tuberculosis (TB), October 2016 will be remembered best as a month that delivered two sobering wakeup calls. First, the World Health Organization (WHO)—citing new surveillance data released by the Indian government—announced that the TB epidemic is larger than previously estimated: TB killed 1.8 million people and caused 10.4 million to fall ill in 2015. Second, Treatment Action Group (TAG) released its 11th annual Report on Tuberculosis Research Funding Trends, showing that funding for TB research and development (R&D) in 2015 fell to its lowest level in seven years, declining by US$53.4 million from the prior year. This juxtaposition between rising estimates of TB mortality and morbidity and diminishing investment in the research required to overcome TB suggests that countries have yet to mobilize in pursuit of the ambitious targets of WHO’s End TB Strategy, which sets a vision to achieve a world free of TB by 2035. The action needed is clear: governments must make deliberate, concerted efforts to overcome the deep funding deficit inherited from the five years preceding the End TB Strategy’s launch. The Stop TB Partnership’s Global Plan to Stop TB, 2011–2015 estimated that the world needed to spend $9.84 billion on TB R&D between 2011 and 2015 to enable the scientific advances in TB prevention, diagnosis, and treatment required to end TB as a public health threat. TAG’s most recent report presents new data on TB research funding in 2015, the fifth and final year of the Stop TB Partnership’s 2011–2015 Global Plan, and, in closing out this five-year reporting period, provides a report card on the plan’s financial and scientific milestones. By both measures, reality fell far short of aspiration. Worldwide, funders invested $3.29 billion in TB R&D from 2011 to 2015, amounting to just one-third of the $9.84 billion target. Instead of narrowing the funding gap, over the five-year period, global investments stalled or fell. Funding declined in three of the past five years, dropping by $36.5 million in 2012, $12.3 million in 2014, and $53.4 million in 2015 (in relation to prior year). The period ended with a lower level of funding than it started ($620.6 million spent in 2015 compared to $675.3 million in 2011; see figures 1 and 2). Compounding this instability, the TB research field remains in the precarious position of relying on just a handful of donors; 57 percent of funding from 2011 to 2015 came from just two organizations—the US National Institutes of Health and the Bill & Melinda Gates Foundation. Over the same period, pharmaceutical industry investments in TB R&D decreased by 40 percent, dropping from $145 million in 2011 to $87 million in 2015.   In addition to tracking funding for TB research, TAG analyzed progress in TB diagnostic, drug, and vaccine development. In each field, advances over the past five years came up short against the 2011–2015 Global Plan’s scientific goals (see figures 3 through 5). For example, TB drug developers set a goal of ending 2015 with 21 compounds in phase 1 clinical trials; in fact, the year ended with only 2. Disappointing results published in 2013 from a phase 2b trial of TB vaccine candidate MVA85A meant that instead of advancing four vaccine candidates into phase 3 trials by the end of 2015 as envisioned, the TB vaccine field redirected efforts to earlier stages of discovery and clinical development. TB diagnostic developers made greater progress, but still ended the period without satisfying the goal of delivering a new test capable of diagnosing drug-resistant TB (DR-TB) in peripheral labs and a test able to predict an individual’s risk of progressing from TB infection to active TB disease. Despite these scientific disappointments and financial shortfalls, the TB research field managed to make several significant advances over the five years including: Conditional approval of two new drugs from novel classes to treat DR-TB (Janssen’s bedaquiline and Otsuka’s delamanid), the first such novel drugs in over four decades. The development of a shorter regimen (3HP) for treating latent TB infection that is safe and efficacious in children and people with HIV and AIDS. The development of several new diagnostic tests, including the rollout of a rapid alternative to smear microscopy (GeneXpert), a simple test (Determine LAM TB) that can identify TB in people with HIV who have very low CD4+ T-cell counts, and several options for diagnosing first- and second-line drug resistance faster than conventional culture (line probe assays). Intensified efforts to study the safety and pharmacokinetics of first- and second-line TB drugs in children. •Significant advances in fundamental understanding of TB biology. Building on these successes in the post-2015 period and putting research on track to meet the long-term goals of the End TB Strategy will require a massive step-up in funding. Most of this additional money will need to come from governments, and this responsibility must be shared by all countries—developed and developing, those with high TB burdens, and those already approaching TB elimination. To this end, TAG has embarked on two advocacy drives to increase public funding for TB research. First, in June 2016, TAG published a policy brief setting the first-ever US government targets for TB R&D funding. The brief calls for US government agencies to spend $300 million on TB R&D by 2017 (enough to pull even with inflation and match 2009 purchasing power) and $400 million by 2020 (enough to outpace the rising costs of biomedical research and increase funding for TB R&D by $72 million in real terms over 2009). Second, TAG is petitioning leaders of the BRICS countries—Brazil, Russia, India, China, and South Africa—to triple their funding for TB R&D, echoing demands first voiced by the hundreds of people who marched with Treatment Action Campaign in support of TB research in Cape Town, South Africa, in December 2015. As those marchers pointed out, the BRICS countries are home to nearly half of the world’s new TB cases and deaths, yet only provide 4 percent of reported funding for TB R&D. We’ll deliver the petition to BRICS country ministers of health when they meet in New Delhi, India, at the 6th Meeting of the BRICS Health Ministers in December 2016. You can join the call by signing on here.

In this guest post, Mike Frick, TB/HIV project officer at the Treatment Action Group (TAG), reflects on activist calls for greater investment in tuberculosis (TB) research and development (R&D) at the 46th Union World Conference on Lung Health and the stagnation of global TB R&D funding at a time of growing drug resistance. Activists march at the 46th Union World Conference on Lung Health in Capetown, South Africa to call for more funding for TB R&D. Photo: David Harrison One city, host to two TB conferences, opened by two marches, held eight years apart. In certain moments at the 46th Union World Conference on Lung Health in Cape Town, South Africa, the present echoed the past. On Friday, December 4, 1,000 people organized by Treatment Action Campaign (TAC) and SECTION 27 marched to the site of the conference to call on governments of the BRICS countries [Brazil, Russia, India, China, and South Africa] plus Indonesia to triple their funding for TB R&D. The sight of so many people demonstrating in support of TB R&D called to mind a moment at the 38th Union World Conference in 2007 when thousands took to the streets of Cape Town demanding greater global investments in TB research and programs. TAC march to demand more funding for research into & the treatment of TB. Photo: David Harrison Seasoned TB activists present at last week’s march likely experienced a feeling of déjà vu. Both marches pointed to the grave lack of investment in TB research. And each occurred at moments their participants described as emergencies. In 2006, an outbreak of extensively drug-resistant TB in Tugela Ferry, South Africa, captured headlines around the world and crystallized how decades of inattention had allowed TB to become more deadly. This year, marchers carried banners reading “We die of TB,” “Invest in TB research,” and “Invest so we can live” (see photos). According to the protest’s organizers, these messages were in response to ten years of data on global funding for TB research collected and analyzed by TAG in a report released on November 29. TAG’s tenth annual Report on Tuberculosis Research Funding Trends shows that after increasing modestly from 2005–2009, funding for TB research has stagnated in the five years since. Over this ten-year period, total funding for TB research has never exceeded more than US$700 million per year (see figure 1). In 2015, worldwide funding for TB R&D totaled $674 million, falling $1.3 billion short of the $2 billion experts estimate the world must spend on TB research each year to eliminate TB. Funding shortfalls have persisted in each category of research tracked by TAG—basic science, diagnostics, drugs, vaccines, and operational research—each of the last ten years, making the last decade one of missed targets and forestalled potential. Credit: TAG Members of TAC and those who marched with them understand that the pace of research to develop new drugs, diagnostics, and vaccines to fight TB is falling behind the spread of drug-resistant TB (DR-TB). The need for better ways to prevent, diagnose, and treat TB has never been greater. TB is now the leading cause of death from an infectious disease, responsible for more deaths each year than HIV and AIDS. In 2014, 400,000 people newly developed DR-TB. TAG’s research suggests that filling the funding gap and accelerating TB research will depend on increasing support from endemic country governments, which is why TAC directed the message of its march to the BRICS countries and Indonesia. Sixty-two percent of money spent on TB research comes from public institutions, a proportion that has grown in the wake of an exodus of pharmaceutical companies from TB research since 2012. Photo:David Harrison Throughout the week, activist voices compelling greater attention to TB research reverberated throughout the conference center. Speaking at the conference’s closing ceremony, Anele Yawa, TAC general secretary, pointed out that 40 percent of TB deaths occur in the BRICS countries, yet these nations give only 3.6 percent of the available funding for TB research. Calling out leaders of the BRICS countries by name, Anele urged them to triple their support for research to overcome a disease that kills so many of their people. “We can’t just tinker and settle for incremental change while our brothers and sisters are dying,” said Anele. “We demand a revolution in funding for TB research.” This call appears to be gaining traction in South Africa. At the end of the march, South Africa’s Minister of Health, Aaron Motsoaledi, accepted a memo endorsed by TAC, TAG, Médecins Sans Frontières, the Global TB Community Advisory Board, HIV i-base, TB Proof, SECTION 27, and the People’s Health Movement. The memo called on governments to declare TB and DR-TB public health emergencies and close the TB research funding gap. In some ways, Minister Motsoaledi’s very presence at the march was a sign of how things have changed since the first march for TB research in Cape Town eight years ago. In 2007, no parliamentarians or ministers of health received the protestors’ list of demands, and the stagnation of TB research funding in the years that followed suggests these earlier cries fell on deaf ears. Political will to support TB research is also gaining traction at the global level. A week before TAG released its report on TB R&D funding, the World Health Organization (WHO) launched the Global Action Framework for TB Research and announced the creation of a TB research focal point within the WHO’s Global TB Programme. Intensified research and innovation is the third pillar of the WHO’s End TB strategy, which aims to eliminate TB by 2035. Through the Action Framework, the WHO aims to advance TB research by building support for TB R&D at the country level, with a focus on low- and middle-income countries that bear the greatest burden of TB but that have traditionally given less than 5 percent of global funding for TB R&D. As part of this initiative, the WHO will work with a group of “pathfinder” countries to develop national strategic plans for TB research backed by concrete milestones over the next five to ten years. It is imperative that these plans are backed by financial commitments that increase TB R&D funding above its current level. Those who marched alongside TAC in Cape Town on December 4 took just the initial steps to build the public pressure and accountability that will be required to make the Action Framework a success and enable the research required to end the TB epidemic—in South Africa and across the world.  

At the 45th Union World Lung Health Conference, TB activists called for more funding for TB R&D. Photo: Steve Forrest/The UnionIn this guest post, Mike Watson Frick—TB/HIV program officer at Treatment Action Group (TAG)—writes about the state of tuberculosis (TB) research funding and civil society actions that took place at the recent Union World Conference on Lung Health in Barcelona, Spain. At the end of last month, the global community of TB scientists, activists, and healthcare workers gathered in Barcelona, Spain for the 45th Union World Conference on Lung Health. For the first time, the conference opened with a rousing call by civil society organizations to triple annual spending on TB research to US$2 billion per year. At the conference's opening ceremony, activists from Treatment Action Campaign (TAC), TAG, the Global TB Community Advisory Board, AIDS Free World, International Treatment Preparedness Coalition, and HIV i-Base called on governments, donors, and industry to #CoughUpTheTBMoney to fully fund TB research and the development of new TB treatments.The activists who took the stage in Barcelona were reacting to the dismal news contained in a report released by TAG the previous week showing that funding for TB research in 2013 fell $1.3 billion short of the $2 billion the Stop TB Partnership estimates the world must spend each year in order to eliminate TB as a public health threat.2014 Report on Tuberculosis Research Funding Trends. Photo: Treatment Action GroupTAG's annual Report on Tuberculosis Research Funding Trends shows that funding for TB research has flat lined since 2009. After declining in 2012, funding for TB research & development (R&D) increased slightly in 2013, due largely to an increase in spending by the Bill & Melinda Gates Foundation. Worldwide, governments, charities, industry groups, and multilateral organizations spent just $676.6 million on TB R&D in 2013. Funding shortfalls persist in every category of TB research tracked by TAG—basic science, diagnostics, drugs, vaccines, and operational research—making 2013 the ninth straight year of missed funding targets. The gap is largest, in absolute terms, in TB drug research where funders spent just $255 million of the $740 million funding target.The human consequences of such anemic funding for TB drug research were voiced by many of the TB patients and survivors attending the conference in Barcelona. At the opening ceremony, two women personally affected by TB read statements about their experiences, illustrating the pressing need to support research. Portia Serote of TAC described the lengthy duration, side effects, and difficulties of receiving drug-sensitive TB treatment, while Stephanie A.—a woman from Los Angeles whose brother has extensively drug-resistant (XDR)TB—described how side effects from XDR TB drugs are causing her brother to lose his hearing, as well as feeling in his hands and feet. For both drug-sensitive and drug-resistant TB, shorter, less-toxic regimens would improve the arduous journey patients must endure to cure their TB.Yet desperately needed progress in TB research rests on a shaky financial foundation rocked by two forces. First, the pharmaceutical industry is abandoning TB research as reflected in the 33 percent drop in industry spending from $144.97 million in 2011 to $99.6 million in 2013. With expenditures under $100 million, the private sector now spends less on TB R&D than it did in 2009 at the peak of the economic crisis. Even more alarming, 60 percent of industry spending on TB research in 2013 came from one just one company: Otsuka. Not considering Otsuka's investment of $58.7 million, other private sector companies mustered just $40 million on research to develop new TB drugs, diagnostics, and vaccines. Three pharmaceutical companies have left TB research in as many years, a rate of attrition driven by an industry-wide shift away from anti-infectives research as pharmaceutical companies either concentrate on more lucrative endeavors—such as developing new vaccines and drugs for chronic diseases or pursuing mergers and acquisitions to focus on core business. The abandonment of anti-infectives work has become severe enough to prompt a Presidential executive order that includes a recommendation to give incentives of $800 million per year for pharmaceutical companies to develop new drugs.Conference participants signed posters with the rallying cry #CoughUptheTBMoney. Photo: Mike Frick/TAGPharmaceutical disinvestment is increasing pressure on public funders to shoulder a greater percentage of TB R&D funding at a time when many government agencies are fighting off the shortsighted cutbacks of fiscal austerity measures—the second force undermining TB research. Federally mandated, across-the-board budget cuts under sequestration in 2013 led to lower TB R&D spending at the US National Institute of Allergy and Infectious Diseases and the US Centers for Disease Control and Prevention—the first and ninth largest funders respectively of TB R&D globally. Sixty-two percent of public money for TB research comes from one country—the United States—revealing the TB research endeavor’s depth of dependency on just a handful of public agencies, whose budgets are either being actively scaled back or, at best, failing to keep pace with inflation and the rising costs of biomedical research.Reducing TB deaths by 95 percent and cutting the number of new TB cases by 90 percent by 2035—the two goals of the post-2015 TB strategy approved by the World Health Assembly (WHA) in May 2013—will require research to develop and introduce new tools. The WHA notes that new tools must be introduced no later than 2025—and preferably sooner. Yet chronic underfunding of TB research jeopardizes this vision of achieving a world free of TB. Reversing this stagnation will require building a movement for TB research that can bring money, muscle, and political commitment to bear on research funders—new and old—from all sectors. The message to #CoughUpTheTBMoney, repeated throughout the meeting in Barcelona and endorsed by hundreds of signatures from conference delegates, represents a small but significant first step toward building a stronger TB research movement.

In this guest post, Mike Frick—project officer at the Treatment Action Group (TAG)—writes about the organization’s new report on funding for tuberculosis (TB) product development. Each year since 2006, TAG has tracked spending on research and development (R&D) for new diagnostics, drugs, and vaccines to improve TB treatment and prevention. The 2013 Report on Tuberculosis Research Funding Trends: 2005–2012 presents eight years of funding data. It also compares current spending in six research areas to the corresponding R&D funding targets outlined in the Stop TB Partnership’s Global Plan to Stop TB, 2011–2015. For the first time, TAG also analyzed investments in pediatric TB R&D. The report finds that after seven years of slow and unsteady increases in funding, TB R&D investors reported a drop in spending in 2012 that threatens to undermine the tenuous gains made since 2005. How much did funding decline? Funding for TB R&D fell by $30.4 million from 2011 to 2012. The $627.4 million spent on TB R&D in 2012 represents just 31.4 percent of the $2 billion annual investment called for by the 2011-2015 Global Plan and leaves a shortfall of $1.39 billion. At $10.3 million, investments in pediatric TB R&D comprised less than 2 percent of total 2012 spending and declined by 12 percent compared with 2011 levels. Where did funding fall the most? Compared to 2011, spending on TB R&D fell in four research categories: Funding for diagnostics fell by 23.4 percent from $55.4 million in 2011 to $42.4 million in 2012, leaving 87.5 percent of the $340 million annual target unfunded. Drug research spending dropped by 6.7 percent from $254.8 million in 2011 to $237.8 million in 2012. This leaves 67.9 percent of the $740 million annual target unfunded. Investments in vaccines declined by 9.3 percent from $95.4 million in 2011 to $86.6 million in 2012, leaving 77.2 percent of the $380 million annual target unfunded. After exceeding the annualtarget in 2011, funding for operational research dropped back below this target amount, declining by 9.8 percent from $85.5 in 2011 to $77.1 million in 2012. Funding for TB R&D fell by $30.4 million from 2011 to 2012. The $627.4 million spent on TB R&D in 2012 represents just 31.4 percent of the $2 billion annual investment called for by the 2011-2015 Global Plan and leaves a shortfall of $1.39 billion. Source: TAG/Hollander Snow Studio Who supports TB R&D? Public sector donors gave 61 percent of the global total, followed by the philanthropic sectorwith 20 percent and the private sector with 18 percent. Multilateral institutions contributed just 1 percent of total spending. The top ten donors disbursed 78 percent of total TB R&D investments in 2012. Two organizations – the National Institute for Allergy and Infectious Diseases (NIAID) and the Bill & Melinda Gates Foundation – each spent over $100 million and together comprise 45 percent of the global total. Public and philanthropic institutions in the United States and United Kingdom continue to underwrite the bulk of TB R&D. The BRICS countries (Brazil, Russia, India, China, and South Africa) remain conspicuously absent from the top 10 list. Top 10 TB R&D Funders in 2012 Including 2012 amount and increase (↑)/decrease (↓) /flat-funding (→) compared with 2011 level 1. NIAID ($169.1 million) ↑ 2. The Bill & Melinda Gates Foundation ($111.6 million) → 3. Otsuka Pharmaceuticals ($60 million) ↓ 4. Other National Institutes of Health (NIH) Institutes and Centers ($36.6 million) ↓ 5. The European Commission ($27.3 million) ↓ 6. Anonymous pharmaceutical company ($22.8 million) ↓ 7. The US Centers for Disease Control and Prevention (CDC) ($18.8 million) ↑ 8. The UK Department for International Development ($16.9 million) ↓ 9. The UK Medical Research Council ($14.8 million) ↓ 10. The Wellcome Trust ($13.4 million) ↑ Will funding continue to fall? The $30.4 million decline may intensify in coming years. This drop does not reflect the impact of sequestration-related funding cuts in the US, which forced the NIH to cut 5 percent ($1.55 billion) of its fiscal year 2013 budget. Sequestration led the CDC to cut support for the Tuberculosis Trials Consortium (TBTC), one of the world’s leading TB drug research networks, by 13 percent. In response, the TBTC closed three clinical trials sites. In a field that has struggled to attract scientific attention and talent for decades, sequestration-related cuts could eliminate critical opportunities for young investigators to build their scientific careers in TB R&D. Will the private sector close this gap? Private sector companies could play a much larger role in TB R&D. Yet, for the first time since 2005, private sector spending declined, dropping by 22.1 percent in 2012 compared with 2011. Pfizer, which contributed $6.3 million to TB drug research in 2011, recently announced the closure of its anti-infectives research division. Other drug companies decreased their investments, including Otsuka, whose TB drug delamanid will soon complete a Phase III trial. Wavering commitments to TB R&D from the private sector will place greater pressure on public institutions just as they begin to face unprecedented budgetary drawbacks. Philanthropic support also remained relatively flat, increasing by just 3.1 percent over 2011. What is the impact of this decline? Decreased funding today will delay the development, approval, and implementation of faster diagnostic tests, better drug regimens, and more broadly protective vaccines that are urgently needed to fight TB, which causes 8.7 million people to fall sick and kills 1.4 million people each year. Donors from all sectors in high-, middle-, and low-income countries must recommit to meeting the funding levels required to accelerate TB R&D and end the global TB epidemic.