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Photo: PATH/Teresa Guillien A new vaccine against Middle East Respiratory Syndrome (MERS) could save human lives by boosting immunity in camels. MERS, a virus that causes an innocuous cold in camels but kills nearly one-third of human patients, is primarily found in the Arabian Peninsula, where camels are common and 12 percent are infected at any given time. While the virus does spread between humans, camel-to-human transmission is believed to be a significant driver of new cases. Not only are camels an important host for the virus, but developing a vaccine for animals is cheaper, and the regulatory review is usually less burdensome than for a human vaccine. The vaccine uses a virus engineered to display the spike protein that defines MERS, prompting the immune system to create antibodies that will protect against MERS. The team vaccinated four camels and used an additional four camels as the control group. Three weeks after vaccination, all eight camels were exposed to the virus. While the camels in the control group all became infected, three of the four vaccinated were protected; it is unclear why the fourth was not. Nature took an in-depth look at the development and testing of Ebola vaccine candidate rVSV-ZEBOV and how it could serve as a model for accelerating the research and development (R&D) of tools for other emerging threats. In less than two years, rVSV-ZEBOV went through multiple rounds of testing, culminating in a successful phase III clinical trial. In the typical timeline, it would take years to obtain regulatory approval for the trial, let alone to conduct it, and it would be performed in a setting with greater existing research capacity. The trial design was significant: the team enrolled nearly 4,000 individuals that were close personal contacts of Ebola patients, and those vaccinated were completely protected, while 16 percent of the control group became infected. By using patients’ contacts, they were able to identify and enroll at-risk individuals quickly. The researchers were also able to review preliminary results in real time, and after the vaccine proved to offer a significant advantage, the team immediately began to vaccinate all participants. The White House released a National Action Plan for Combating Multidrug-Resistant Tuberculosis (MDR-TB) last week, with clear actions to be implemented by the US government over the next five years. The Plan is comprised of three goals: (1) Strengthen domestic capacity to combat MDR-TB; (2) Improve international capacity and collaboration to combat MDR-TB; and (3) Accelerate basic and applied Research and Development to combat MDR-TB. The first two goals call for increased diagnosis and treatment of MDR-TB patients while the third calls for R&D for new vaccines, drugs, and rapid diagnostics. Within the third goal, the plancalls for R&D of new products as well as research to improve the use of existing drugs; the development of strategies to identify the "most promising drug and vaccine candidates" within a given portfolio; and the identification of biomarkers (which are an early sign indicating whether a drug or vaccine will be successful) to accelerate clinical trials. Scientists have genetically engineered male mosquitoes whose female offspring will be infertile in order to reduce the population of mosquitoes that transmit malaria in sub-Saharan Africa. Normally, only half of an organism’s offspring inherit a non-dominant gene, however, the team used an approach called “gene drive” to ensure the trait—infertility—will be passed on at a rate of 90 percent. Gene drive involves using an endonuclease—a molecule that literally cuts DNA—to damage the original gene; the cell then duplicates the remaining, engineered gene, which results in two copies of the gene with the desired trait. While vector control is a cornerstone of existing malaria programs, there are concerns that this technique of drastically reducing the mosquito population could have unintended ecological consequences.

As 2015 draws to a close, the Global Health Technologies Coalition is reflecting on the past year in global health innovation. Below, in no particular order, are our picks for the top global health research and development (R&D) news and stories that shaped 2015. First ever vaccine against dengue virus approved The world’s first vaccine against dengue fever was approved by the national regulatory authority of Mexico, marking an important initial step in preventing this mosquito-borne infection, which is spreading worldwide. Nearly half the world’s population now lives in dengue-endemic countries, and an estimated 390 million infections occur each year. The vaccine’s developer Sanofi spent over 20 years and US$1.65 billion developing the vaccine and is now pursuing regulatory approval in 19 other countries. Sanofi has stated it will make the vaccine available for sale at a “fair, affordable, equitable, and sustainable price.” NIH finally receives funding boost Christmas came early for the US National Institutes of Health (NIH). After years of stagnated funding, NIH—the world’s leading public funder of neglected disease R&D—will finally receive a funding boost in 2016. In the fiscal year 2016 omnibus spending package, Congress approved a $2 billion—nearly 7 percent—increase in funding for NIH from $30 billion to $32 billion. NIH has lost 22 percent of its purchasing power since 2003 due to inflation, so this boost will provide critically-needed funding for the agency to continue to build upon its record of leadership in global health R&D. Photo: PATH/Satvir Malhotra Availability of the first child-friendly, appropriately-dosed TB medicines announced Health workers will soon have a critically-needed new tool to improve treatment for the one million children infected with tuberculosis (TB) each year. In November, TB Alliance and partners announced that the first-ever appropriate, child-friendly tuberculosis (TB) medicine in the correct dose will be available in early 2016. At the moment, TB medicines are not available in appropriate doses for children, so parents must crush or cut the pills to administer. This arduous process—combined with the bitter taste—leads to poor adherence. The new treatments are strawberry- and raspberry-flavored, appropriately-dosed versions of the three most commonly used TB medicines. These new treatments are expected to significantly improve TB treatment and adherence among children. Global Health Innovation Act passes House An important new piece of global health legislation championed by GHTC—the Global Health Innovation Act—passed the US House of Representatives earlier this month. This legislation would strengthen global health R&D programming at the US Agency for International Development (USAID) by directing USAID to incorporate R&D across its global health programming and requiring the agency to report annually to Congress on its R&D programs and activities. In 2016 the hard work will begin again to get the Senate to introduce and pass companion legislation so the bill can move another step closer to becoming US law. Ebola product development advanced at lightning speed After years of slow and stunted progress in the development of drugs, vaccines, and diagnostic tools to fight Ebola, product development jumped forward by leaps and bounds in 2015. Thanks to the collaboration of developers, regulatory agencies, and the World Health Organization, six Ebola diagnostics were developed and deployed in West Africa under emergency measures, early-stage clinical trials are underway for at least two Ebola drug candidates with others in development, and at least 15 vaccine candidates are in development with two candidates undergoing Phase II/III trials. The most advanced vaccine candidate VSV-EBOV was shown to offer near-total protection, according to preliminary data analysis from the trials. While these products arrived too late to have a major impact during the epidemic, the accelerated development approaches and mechanisms used may be able to be emulated to speed product development in the future. New pediatric malaria treatment receives positive scientific opinion paving path for regulatory approval A new pediatric malaria medicine— Pyramax® Granules—will soon be available for children worldwide. In November, Pyramax® Granules received a positive scientific opinion from the European Medicines Agency (EMA) under Article 58, a mechanism which facilitates regulatory approval of the product in malaria-endemic countries. The medicine, which was developed by Medicines for Malaria Venture (MMV) in partnership with Shin Poong Pharmaceutical Co. Ltd, is a combination of two antimalarials and is designed to be easy for children to consume. It is taken in liquid form and is flavored to mask the bitter taste. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. Several promising global health products advancing through development The pipeline of global health technologies is growing and maturing with several exciting products moving through critical development stages. For example, a new medicine for drug-resistant TB became the first new TB drug to advance into clinical trials in six years when it entered Phase I trials in February, a vaginal microbicide containing a novel antiretroviral drug to prevent HIV entered Phase I trials in November, a drug candidate with the potential to become the first ever, oral-only, single-dose treatment for sleeping sickness completed Phase I trials in September, and a microbicide vaginal ring is completing Phase II trials with results expected in early 2016. Due to increased attention and investment over the last 15 years, there are now nearly 500 neglected disease product candidates in the pipeline. Global goals recognize importance of health R&D In September, global leaders ratified a new set of global goals, called the Sustainable Development Goals (SDGs), which will guide global development efforts for the next 15 years. GHTC was excited to see these goals recognize the importance of global health R&D with inclusion of a target supporting R&D of vaccines and medicines for diseases primarily affecting developing nations. It’s been broadly recognized that we cannot reach the ambitious SDG health targets—to reduce maternal and child mortality and end the epidemics of HIV/AIDS, TB, and neglected tropical diseases— by 2030 with the health technologies we have today. Now that the goals and targets are in place, accountability is key. We must ensure the SDGs translate into greater investment and political commitment from all nations to catalyze development of the next generation of health technologies needed to transform global health.

Photo: Neil Brandvold/DNDi Global Health Now took an in-depth look at the flesh-eating fungus mycetoma—which enters the body through cuts, and can result in swollen, deformed limbs—in a three-part series on this Untold Global Health Story of 2015. The final installation focuses on GHTC member Drugs for Neglected Diseases initiative (DNDi), a product development partnership that will be initiating a clinical trial in mid-2016 to assess the safety and efficacy of the antifungal Fosravuconazole against mycetoma. Fosravuconazole is currently under development by Japanese pharmaceutical company Eisai, where it has proven more successful at combatting mycetoma in petri dishes than currently used medicines. The leading treatment, itraconazole, is only curative for one in thirteen patients after a year of use. The article notes that DNDi’s entire budget for the study is under US$2 million, compared with the average $1 billion spent by pharmaceutical companies. Eisai has agreed to donate Fosravuconazole pills for the trial which will compare Fosravuconazole, itraconazole, and a placebo. Pharmaceutical company Gilead Sciences has been heavily criticized for “price gouging,” charging Americans $1,000 per pill for their drug sofosbuvir, which, for most patients, cures Hepatitis C in twelve weeks. However, in Egypt, where 10 percent of the population has chronic Hepatitis C—the highest rate worldwide—Gilead is selling them to the government for $10 per pill. The reduced price comes at a cost: to prevent the drugs from entering the black market and undermining Gilead’s sales, the Egyptian government has agreed to several restrictions that some advocates consider humiliating for patients and/or unethical. Not only are the drugs only sold at official government pharmacies, but patients must break the seal and take the first pill on-site to receive their first bottle and must return the original bottle to receive refills. The program has generated interest from other pharmaceutical companies, and the government has entered into similar deals with Bristol-Meyers Squibb and AbbVie, importing their medicines Viekira and Daklinza, respectively. Over the past year, more than 125,000 Egyptians have been treated, and the government hopes to treat another 300,000 each year starting in 2016, with the ultimate goal of reducing prevalence to 2 percent by 2025. Figure 1: Compounds included in the Pathogen Box, by disease (Photo: MMV) GHTC member Medicines for Malaria Venture (MMV) launched the Pathogen Box, a set of 400 compounds, each with proven activity (i.e., in test tubes) against neglected diseases, free for researchers and laboratories around the world. To create the Pathogen Box, MMV's team of chemists, as well as partners with expertise across neglected diseases, evaluated compounds in the European Bioinformatics Institute’s open access database, to determine those with the most potential. The team then acquired fresh samples of each compound to include in the boxes themselves. By expanding access to these samples, the Pathogen Box eliminates a major barrier to drug discovery for malaria, tuberculosis, schistosomiasis, Chagas, and other neglected diseases (See Figure 1).

Photo: PATH/Patrick McKernUpdate: The Global Health Technologies Coalition is excited to announce that the Global Health Innovation Act (H.R. 2241) passed the House of Representatives on December 18. Last month, Representatives Albio Sires (D-NJ) and Mario Diaz-Balart (R-FL) introduced a new piece of legislation—the Global Health Innovation Act (H.R. 2241)—that would strengthen global health research and development (R&D) programming at the US Agency for International Development (USAID).USAID plays an important role in advancing global health in low and middle-income countries and this legislation would ensure that the agency is taking appropriate steps to incorporate innovation for new global health technologies across its programming by requiring that the agency submit an annual report to Congress on the development and use of global health innovations in the agency’s programs, projects, and activities.The Global Health Innovation Act marks a key opportunity in advocacy for the need for innovation in global health. The GHTC dissects the bill below and highlights the key provisions.If passed, H.R. 2241 would: Make permanent and improve USAID’s annual report to Congress on health-related research and development activities. The act would require a comprehensive analysis of USAID’s activities to develop, advance, introduce, and scale up global health technologies. This allows policymakers and advocates to track and understand the full scope of health R&D activities taking place at USAID, identify best practices, and zero-in on gaps that may exist. Require USAID to articulate how it sets goals for health product development and measure progress toward these goals. The legislation would require USAID’s report to describe how it sets goals for health R&D in relation to its overall health objectives and mission, and how the agency measures progress towards these goals. This provides enhanced transparency into USAID’s decision-making and review processes. Require USAID to describe and demonstrate the impact of its investment in health innovations on global health outcomes. This includes analysis in the annual report of how the agency’s investments and activities in health innovation have advanced its goals to reduce the burden of HIV and AIDS, end preventable child and maternal deaths, and protect against infectious diseases. Such an impact analysis will help magnify the importance of investment in health R&D for achieving sustainable health solutions. Direct USAID to report on how it is working with partners, donors, and through public-private partnerships to leverage US investments to accelerate health innovation. This includes a description of the how the agency is working through partnerships to develop, introduce, and scale up affordable, available, and appropriate health products and close gaps in the health innovation development pipeline. This section of the report will acknowledge the diverse coalition of private sector, nonprofit, foundation, and academic institutions partnering with USAID on health innovations, and demonstrate the importance of a coordinated, cross-sector approach to health R&D. Encourage USAID to improve collaboration and coordination, both within USAID and between other US agencies, to fill critical R&D gaps. The act requires that USAID report on how it is coordinating R&D activities across its programs and how it is collaborating with other US agencies to support global health product development and ensure critical gaps are filled. This will help promote a whole-of-government approach to health R&D, which will better leverage investment, knowledge, and expertise. The legislation would make permanent and improve USAID annual report to Congress on its R&D activities. Credit: USAID The Global Health Innovation Act would not only ensure important information about USAID’s activities is made available to global health nongovernmental organizations, advocates, and policymakers in Congress, but it would also be an asset for USAID. In codifying the report on global health innovations, the bill will ensure that the agency continues to coordinate, streamline, and organize its use and development of global health technologies—a practice area that spans many departments and bureaus. It will also help the agency gauge performance, share best practices, and understand gaps in service to more efficiently and effectively serve its mission.The legislation draws upon the 21st Century Global Health Technology Act, legislation introduced in the 113th Congress, which sought to strengthen global health R&D programming at USAID by codifying programs supporting product development partnerships. The new legislation takes a more holistic approach, and directs USAID to analyze how it is using innovation to address global health challenges and the ways in which the agency can further accelerate the development and use of health technologies. It shifts away from endorsing specific programs and instead underscores the importance of USAID’s strong partnerships that leverage investments in R&D and advance global health innovation.Passing the Global Health Innovation Act will drive home the fact that health innovations are a critical piece of the global health agenda. GHTC and our members look forward to working with Congress to champion this important legislation.To read the full text of the Global Health Innovation Act, click here.