Breakthroughs Blog: Tuberculosis

In this guest post, Jamie Rosen—media and communications manager at Aeras—writes about a new film series that features personal stories of people affected by tuberculosis (TB) worldwide, and the urgent need to develop new vaccines and other tools against the disease. Aeras is excited to share the trailer for a series of short films exposing the underreported global epidemic of TB and the movement for innovation to improve our tools to fight it. In the TB community, as in other areas of global health, we are constantly seeking ways to help people comprehend the scale and the individual tragedy of this disease, to understand the difficulties of treating it, and to inspire people to do what it takes to adequately address it. Aeras has been working with filmmaker Mo Scarpelli and her crew over the past several months to produce four films. Each film will focus on the story of one individual interspersed with expert interviews, and will feature footage from five countries around the world. The first film will focus on an American multi-drug resistant TB survivor; the second on an Indian TB doctor; the third on a South African woman who volunteered for a clinical trial; and the fourth on a British researcher working to develop new TB vaccines. Aeras is grateful for the advice and participation of many people who are working tirelessly to take care of today’s TB patients and foster hope for a better future—one with more effective diagnostics, drugs and ultimately vaccines against this rapidly evolving disease. If this trailer inspires you, please go to www.aeras.org and spread the word. For more information or to organize a screening, please contact Jamie Rosen at jrosen@aeras.org.

In this guest post, Molly Schmalzbach—public affairs analyst in the Office of HIV and AIDS at the US Agency for International Development (USAID)—discusses the agency’s support for research to develop new HIV and AIDS and tuberculosis (TB) products. This post is the first in a series highlighting USAID’s new strategy for global health research and development (R&D). It originally appeared on the IMPACT blog. Nearly all great scientific advances can be traced back to methodical R&D. R&D is a critical step in meeting goals and achieving health results that are cost-effective, sustainable, and grounded in evidence. In December 2012, USAID released its new strategy for global health R&D. The report outlines how the agency plans to address some of the world’s most challenging health and development issues through new technologies, research, and evaluation, as well as the scale-up of interventions backed by scientific evidence. HIV and AIDS is a large component of this effort, and the agency—through the US President’s Emergency Plan for AIDS Relief (PEPFAR)—is supporting very promising HIV research in several areas, including microbicides, vaccines, and diagnostic tools to detect TB in HIV-positive patients. Microbicides: Microbicides are substances that can be applied vaginally or rectally to reduce the risk of HIV transmission during sex. Vaginal microbicides are a particularly desirable innovation because women can use these products on their own to protect themselves from HIV infection. Given that women make up almost 60 percent of people living with HIV in sub-Saharan Africa and struggle to negotiate other HIV prevention methods—such as condoms—with their partners, USAID supports microbicide R&D as a key intervention in reaching an AIDS-free generation. Women can use this ARV-based vaginal gel to protect themselves against HIV. Photo credit: International Partnership for Microbicides. In 2010, the CAPRISA 004 clinical trial showed that a vaginal microbicide made up of 1 percent tenofovir gel (a topical form of the antiretroviral drug) protected women against HIV. Following this success, a new public-private joint venture, known as Propreven, is preparing to obtain regulatory approvals, create manufacturing capacity, and support product distribution of tenofovir gel in various African countries. Two additional studies are also underway—the FACTS 001 clinical trial, which is a follow-on to CAPRISA 004 and is currently in year two, and the CAPRISA 008, a study that is examining and addressing implementation issues for future microbicide programs. Both of these studies are supported by a US and South African partnership made up of USAID, the Bill & Melinda Gates Foundation, and the Government of South Africa. Vaccines: While microbicides are an important method in preventing HIV when tailored to specific populations, no single approach is likely to have as dramatic an impact on the HIV pandemic as an effective vaccine. That is why USAID has supported HIV vaccine R&D through the International AIDS Vaccine Initiative (IAVI) since 2001. IAVI is a public-private product development partnership that acts as a virtual pharmaceutical company to accelerate the development and clinical testing of HIV vaccine candidates. On the vaccine design front, IAVI and its partners in the Neutralizing Antibody Consortium (NAC) have designed four new immunogens—the active ingredients of vaccines that stimulate the immune system—and are testing these structures as part of potential HIV vaccines. Two clinical trials involving IAVI’s work are examining new HIV vaccine regimens. One trial nearing completion in East Africa is evaluating a vaccine regimen that uses a new technique called electroporation, and some exciting results are expected in the coming year. Electroporation applies a small charge to effectively distribute the contents of the vaccine in the muscle and enhance uptake of the DNA. Another trial poised to begin within the next few weeks will evaluate new viral vectors carrying HIV antigens. TB Diagnostics: Microbicides and vaccines are critical priorities for USAID’s HIV prevention efforts; however, we must also provide care and support to people already living with HIV. Since TB is the leading cause of death among HIV-positive people, USAID supports the coordination of TB and HIV services to better care for people living with each disease. In recent years the prevention, diagnosis, and treatment of TB has become more complicated because of two factors: HIV-associated TB and multidrug-resistant (MDR) TB. HIV-associated TB often goes undetected because the most common TB diagnostic, called sputum smear microscopy, is not very effective in people infected with HIV. The Cepheid Xpert is a rapid TB diagnostic and sensitive to HIV-associated TB. Photo credit: Cepheid. Fortunately, there is a promising new diagnostic for TB, including HIV-associated TB, on the horizon! This rapid and sensitive test, called the Cepheid Xpert MTB/RIF® assay, has the potential to revolutionize the diagnosis of TB. While Xpert still faces some operational and programmatic barriers, such as high costs and the need for a sustained power supply, USAID has already begun supporting the roll-out of this new tool by helping countries obtain Xpert machines, designing associated policy guidance and strategies, and developing technical approaches to guide implementation. R&D in these three key areas is what keeps USAID at the forefront in the fight against HIV and AIDS. As David Stanton, the director of the Office of HIV and AIDS at USAID said, “These clinical trials and new technologies have the potential to dramatically change the HIV and AIDS landscape and reverse the trajectory of the global HIV pandemic.” To learn more about USAID’s strategy for global health R&D in the coming years, be sure to check out our latest Report to Congress: Health-Related Research and Development Strategy 2011-2015.

The New Year has brought some much-needed good news in the fight against tuberculosis (TB). The US Food and Drug Administration (FDA) recently announced that it has approved a new treatment for multidrug-resistant TB that can be used as an alternative when other drugs fail. The approval is the first time in 40 years that the FDA had approved a drug that attacks TB in a different way from currently available treatments. The new drug, bedaquiline, is made by Janssen Therapeutics. It will be sold under the brand name Sirturo, and is the first drug developed specifically to treat multi-drug resistant TB involving the lungs. Sirturo was approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug will likely benefit patients in need. According to the FDA, this program provides patients earlier access to promising new treatments while the drug developer conducts additional studies to confirm the drug’s benefits and safety. The FDA has approved a new treatment for multidrug-resistant TB that can be used as an alternative when other drugs fail. The approval is the first time in 40 years that the FDA had approved a drug that attacks TB in a different way from currently available treatments. Photo credit: PATH. A study in September in The Lancet found that almost 44 percent of patients with TB in countries like Russia, Peru, and Thailand showed resistance to at least one second-line drug. “Multidrug-resistant tuberculosis poses a serious health threat throughout the world, and Sirturo provides much-needed treatment for patients who have don’t have other therapeutic options available,” Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said. Given that the standard drugs used to treat the disease were developed in the 1950s and 1960s, it is no surprise that the TB bacterium has become more and more resistant to these older drugs over the past 50 years. There is a pressing and urgent need for even more new TB drugs, which makes this new FDA approval so significant. It is also noteworthy that the FDA approved Sirturo under its accelerated approval program, in addition to granting the drug fast track, priority review, and orphan-product status. Beyond the lifesaving benefits of the drug itself, these FDA programs resulted in quicker access to this much-needed new TB drug and should serve as models for other drugs desperately needed around the world. It’s critical that the FDA continues to support its priority review, fast track, and similar programs, which can help speed access to safe and effective global health drugs. It’s equally critical that Congress provides the FDA with sufficient funding to carry out this global health work. With the threat of sequestration—which would result in a cut of $318 million for the FDA—still looming, policymakers in Congress must prevent sequestration and protect FDA’s global health activities. Otherwise, approvals for new global health drugs like Sirturo could suffer. “There is no question that we need more and better treatments for drug-resistant TB. And we’ll continue to need new drugs as the disease mutates or changes,” FDA Commissioner Margaret Hamburg wrote in a blog post about the approval. “Meanwhile, Sirturo is a welcome addition to the drugs that we have available to treat patients who have multi-drug resistant TB who need this drug as part of their treatment regimen.”

In this guest post, Eleonora Jiménez-Levi—senior researcher at the Treatment Action Group (TAG)—writes about the latest report on the state of funding for tuberculosis (TB) research and product development. Mycobacterium tuberculosis (MTB) is one of the oldest known human pathogens that continues to pose a global public health threat in the 21st century. The World Health Organization reports that MTB—the bacterium that causes TB disease—was responsible for 1.4 million deaths in 2011, including 430,000 deaths among people with HIV. Current strategies and tools cannot effectively prevent and control TB. BCG, the only vaccine approved for TB, is over 100 years old. BCG cannot offer protection against pulmonary TB, and cannot be used among HIV-positive infants. The most widely used diagnostic tool—sputum smear microscopy—detects roughly 50 percent of pulmonary TB cases, and fares far worse among people with immature or compromised immune systems. Treatment against drug-sensitive TB involves 6–9 months of first-line drugs, and drug-resistant TB requires 20 months or more. The lengthy treatment regimen results in suboptimal and, at times, deadly outcomes because of several challenges including difficulty of adhering to treatment, drug stock-outs, toxic side effects, treatment costs, and incompatibility between TB drugs and antiretroviral medicines for people with HIV. A doctor examines the chest x-ray of a TB patient. Photo credit: PATH. For the seventh year, TAG and the Stop TB Partnership have published the latest investment data and analysis on the state of global TB research and development (R&D) funding. The 2012 Report on Tuberculosis Research Funding Trends: 2005–2011 builds on seven years of investment data to report on annual funding trends and gaps among the leading TB R&D donors. The report analyzes current spending levels across six research areas to assess how they compare to the R&D funding targets in the Global Plan to Stop TB 2011-2015. The new report found that in 2011, 81 donors invested $649.6 million in TB R&D. This is an 82 percent increase from the baseline year of 2005, but only a 3 percent increase over 2010 funding. The top ten donors disbursed $506.7 million of the $649.6 million total, or 78 percent of the global share. Despite the small funding increase observed between 2010 and 2011, the world continues to fall $1.35 billion short of the annual $2 billion funding target recommended by the Global Plan. To accelerate global TB R&D and capitalize on the scientific gains achieved in the last decade for drug, vaccine, and diagnostic development, more financial resources are needed, particularly in: Biomarker discovery to modernize TB drug and vaccine development by demonstrating the progress and effects of treatment or immunity early on, which in turn radically reduces the time and costs of the clinical trials. Biomarker discovery for the development of a point-of-care diagnostic test that can identify people with latent TB at risk of developing active TB, as well as biomarkers associated with infection, treatment response, cure, and drug susceptibility or resistance. TB sample banks that support biomarker discovery with well-characterized specimens. Late-stage drug and vaccine clinical trials, many of which will take place in high-burden countries with limited laboratory capacity or infrastructure that meet good clinical practice standards. Basic science research to enhance our scientific understanding of TB disease and the MTB pathogen. The global TB community should also give further consideration to: Establishing access plans to optimize the rational use of new TB drugs and regimens when they become available, as well as prevent the emergence of resistance to new TB treatments. Developing pediatric investigational plans to ensure child-friendly formulations are available as quickly as possible. Conducting drug-drug interaction studies for novel TB drug regimens. Providing compassionate use and expanded access, which are particularly important for people with drug-resistant TB who have limited treatment options. Modernizing TB regulatory guidelines and streamlining regulatory requirements across and within regions. All of these recommendations and more can be accomplished if policymakers, researchers, activists, clinicians, donors, implementers, and people affected by TB pledge their commitment to achieve zero TB deaths, zero new TB infections, and zero suffering from TB. The Zero Declaration, created by a worldwide group of TB stakeholders in June 2012, is a new strategy that calls on the international community to embrace a “new global attitude in the fight against TB … and mobilize sufficient political will and resources to prevent needless transmission, sickness, and death.” The goal of the campaign is to organize and inspire people to work toward eliminating TB as a public health threat with greater urgency, more political will, and increased investments. Promising new tools are on the horizon, but without political will and adequate funding to support the development of new vaccines, diagnostics, and drugs, the world will not be able to contain the growing problem that drug-resistant TB poses, much less eliminate TB as a public health threat by 2050.