Breakthroughs Blog: Congress

Office of Management and BudgetLast Thursday, the Trump Administration released an outline of its budget proposal for fiscal year (FY) 2018, proposing dramatic cuts to US agencies involved in global health research and development (R&D) including the State Department (State) and US Agency for International Development (USAID) and the Department of Health and Human Services (HHS), including the National Institutes of Health (NIH). If enacted, these cuts would have significant impact on programs that advance global health innovation and protect the world and Americans from global disease threats. As an introduction to the Trump Administration’s budget priorities, this short and “skinny” budget outline lays out only high-level issues and proposes spending levels for top-line accounts. A more detailed funding proposal is expected in May that will include funding levels for individual agencies and programs. Still, while short on detail, the proposal is clear on targets for proposed reductions: the budget calls for nearly a one-third reduction in funding to State and USAID (cuts of $10.1 billion) and an 18 percent reduction in overall funding for HHS (cuts of $15.1 billion). Within HHS, a one-fifth reduction in funding (cuts of $5.8 billion) is proposed for NIH. The only US agency involved in global health R&D to receive a proposed increase in funding is the Department of Defense (DoD)—which is proposed to receive a 9 percent ($54 billion) boost. It remains unclear whether any of this increased funding would be directed to medical and infectious disease research. Reading between the lines, the President’s “skinny” budget foretells a challenging funding climate for global health R&D at State, USAID, and HHS: State Department and US Agency for International DevelopmentFunding for State and USAID was among the hardest hit in the President’s proposed budget. The blueprint calls for a 28 percent cut to State and USAID base funding, which grows to 30 percent when reductions to overseas contingency funds are included. USAID is a critical component of the US government’s support for global health R&D: In 2015, USAID provided nearly US$80 million in funding to support global health R&D. Cuts to USAID funding could stall promising innovations under development and halt efforts to roll out new technologies in USAID programs. While the President’s proposal does express support for US global health initiatives including the President’s Emergency Plan for AIDS Relief (PEFPAR); the Global Fund for AIDS, Tuberculosis and Malaria; Gavi, the Vaccine Alliance; and US malaria programs; the level of support proposed for these programs remains unclear. Language in the blueprint does not indicate if these programs would continue robust or expanded activities, or indicate whether these programs would be supported at current funding levels. It is also important to note that not all global health programs were called out in the budget, leaving uncertainties about how critical programs supporting maternal and child health, nutrition, tuberculosis, and neglected tropical diseases will be prioritized by the Administration. The budget also articulates a dramatic overall shift in America’s approach to diplomacy and development assistance with specific proposals calling for consolidation of State and USAID activities, linking aid and assistance to strategic interests, and reducing funding for the United Nations and affiliated agencies. It will be important to continue to monitor the impact of these proposals. Department of Health and Human Services The Administration’s budget proposes an 18 percent reduction to HHS funding across the board—cuts that if enacted would bring HHS to its lowest level of funding in nearly two decades. This would significantly reduce funding for HHS agencies engaged in global health R&D, including NIH, the US Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the Biomedical Advanced Research and Development Authority. Not only would cuts of this level have real impact on ongoing and future research needs, they could also undermine America’s leadership in global health R&D and diminish our ability to prevent, detect, and respond to emerging health threats. A full picture of the President’s proposal for HHS is not yet available, but limited details follow below: National Institutes of Health The President’s budget proposes a 19 percent cut to the NIH budget. NIH leads the world in financial support and technical expertise for global health R&D—so cuts of this magnitude would have a detrimental and lasting global impact on ongoing and future research projects. The budget also proposes a reorganization of NIH Institutes and Centers and calls for the elimination of the Fogarty International Center. Fogarty plays an important role in global health R&D. Its programs build partnerships between US and international researchers and strengthen the capacity of scientists in low-income countries to address critical global threats like HIV and AIDS, Ebola, and other emerging infectious diseases. Calls to eliminate this center are concerning. Cutting the Fogarty Center—a small center with a $70 million budget—would save little in the overall federal budget, while increasing our vulnerability to global disease threats. The President’s blueprint also calls for a “rebalance” of federal contributions to NIH research funding, which warrants careful consideration and further monitoring. If NIH research priorities are shifted to align only with disease burden in the United States—as is sometimes proposed—important research on neglected diseases and conditions will be jeopardized, ceding US leadership in this arena and potentially leaving Americans more vulnerable to infectious and emerging disease threats. Centers for Disease Control and Prevention and health preparedness The President’s budget proposal does not include overall funding levels for CDC, nor does it call out specific CDC programs for support or reductions. However, given the magnitude of cuts in the overall HHS budget, it is clear CDC funding is also at risk. The only CDC mention in the blueprint is a proposal to shift $500 million in CDC funding to block grants to be administered by the states. While details on this proposal are scarce, it’s likely these funds would be repurposed from within CDC’s budget, rather than represent new funding. CDC leads the United States’ public health defense system against infectious diseases, so robust funding for the agency is a global health and national security imperative. The agency plays a unique and important role in global health R&D by developing new tools and techniques for disease surveillance, training researchers and health workers overseas, and developing new health tools to advance disease detection, prevention, and response efforts. The budget also proposes the creation of a new Federal Emergency Respond Fund to enable rapid response to public health threats like Zika or Ebola. Such a dedicated fund has been championed by many public health leaders, including former CDC Director Tom Frieden. However, in the President’s request, there are few details regarding the fund’s approach or operations. It remains unclear how large the fund would be, whether it would support preventative R&D, or whether funding for the program would come at the expense of current US government emergency response and preparedness initiatives. As the budget proposal also call for reforms to “key public health, emergency preparedness, and prevention programs” under HHS—which could include CDC and other global health security programs—there remains more questions than answers. Food and Drug Administration The FDA also plays an important role in global health R&D by facilitating the review of new global health products to ensure they are safe and effective before entering the market. While the President acknowledged the need to direct more funding to the FDA, the budget blueprint does not propose increased government support for the agency, but rather calls for doubling user fees paid by healthcare companies for the regulatory review of their products—from $1 billion to $2 billion. Noting the constrained budget environment, the proposal says that companies benefiting from FDA approval “can and should pay for their share.” In addition to user fee increases, the Administration also proposes to take new, unspecified actions to speed the development and approval process for drugs and other medical products. Patient advocate groups and the private sector alike have stressed their belief that current review procedures appropriately balance thorough review of safety and efficacy with efforts to expedite products through the review process. Department of Defense The Presidential budget proposes a 9 percent ($54 billion) increase to discretionary funding for DoD. DoD plays a critical role in R&D for infectious diseases; however, the budget blueprint does not address DoD’s medical research activities and provides little information about what increased defense funding may be targeted. Congressional response and next steps The President’s budget proposal is the first official declaration of policy and spending priorities for the Administration and marks the beginning of months of discussions within Congress and the Administration on how best to allocate funds. Congress ultimately controls government spending, and many members on both sides of the aisle have expressed skepticism or criticism about the Administration’s budget blueprint, including its proposed cuts to foreign assistance and medical research. While there are calls in Congress to reduce government spending, and we may see cuts to US agencies engaged in global health R&D, the spending bills passed by Congress will likely look much different than the President’s proposal. GHTC will continue to monitor the FY18 budget and appropriations process and advocate for robust funding for all programs that support global health R&D.

Earlier this year, the World Health Organization (WHO) declared the outbreak of Zika in Latin America a Public Health Emergency of International Concern. The virus, spread by the Aedes aegypti mosquito, was once considered innocuous, causing a mild illness and lasting for only a handful of days. However, the virus has since been linked to devastating birth defects and neurological complications and has spread to more than 60 countries. The virus’s virulence took the research community by storm: although it was discovered in 1947, only 25 scientific papers were published on the topic prior to the current outbreak. As the scientific community learns more about the virus and the disease, the need for tools to prevent, detect, and treat it has become undeniable. On February 22, US President Barack Obama submitted a request to Congress for US$1.9 billion in emergency funding to combat the virus, a critical move, as the US government is unrivaled as the largest funder of global health research and development (R&D). However, 146 days later, Congress has yet to reach a deal, and the US agencies leading the fight against Zika are running out of money. In the meantime, these agencies have made impressive strides in advancing Zika R&D using limited funding and leveraging cross-sector partnerships. An unprecedented number of private-sector partners have also entered the hunt for Zika countermeasures, building out a robust pipeline in record time. Below, we highlight the most promising vaccine, drug, and diagnostic candidates as well as vector control approaches. Vaccines There are currently more than 35 Zika vaccine projects underway, and at least 3 have completed successful animal trials. Inovio Pharmaceuticals and GeneOne Life Sciences partnered to develop a DNA-based vaccine, using a unique delivery approach—electroporation—in which a device is applied to the injection site, sending out electrical pulses that enhance the vaccine’s ability to enter human cells. The vaccine successfully prompted an immune response, including the production of protective antibodies, in both mice and monkeys. In late June, the experimental vaccine became the first to be approved for human clinical trials by the US Food and Drug Administration (FDA). The phase 1 trial, which will enroll 40 healthy adults, is intended to evaluate the safety and tolerability; however, the team will also monitor its ability to induce an immune response. Meanwhile, two more vaccine candidates have proven effective in mice. The candidates include a DNA-based vaccine and one composed of an inactivated version of the Zika virus, the first supported by the US National Institutes of Health (NIH) and the second developed by the US Walter Reed Army Institute of Research. The latter will be tested in phase 1 clinical trials by the US National Institute of Allergy and Infectious Diseases and then transferred to French pharmaceutical company Sanofi for further clinical development. Sanofi is also working on a vaccine of its own; however, it won’t enter clinical trials until 2017. After several months of feasibility studies, British pharmaceutical company GlaxoSmithKline has announced that it will be partnering with the NIH to test its RNA-based vaccine in animals. To date, no DNA or RNA vaccines have been approved for use in humans, although they are often called the future of vaccines. Drugs Due to the dearth of knowledge about the virus and the difficulty of conducting clinical trials and using novel drugs in pregnant women—a key target population for Zika control—the WHO has stated, “It is unlikely at this stage that therapeutics will constitute a priority activity.” However, efforts are underway, both to discover novel treatments and to repurpose existing medicines. Australian biotech company Biotron announced recently that two compounds in their library have proven effective against Zika in test tubes. They will continue to conduct laboratory tests to better assess the safety and efficacy of the compounds in humans. Researchers at the US National Center for Advancing Translational Sciences are screening their compound library—with half a million entities— and have identified a novel drug, which is safe for use in humans and currently in clinical trials for cancer, that prevented the virus from killing progenitor cells, which play a critical role in the neurological system and fetal development. Researchers at the University of California, San Diego are embarking on an ambitious study to virtually screen more than 20 million compounds against the virus. The program—OpenZika—uses a research collaboration platform to harness the power of volunteers’ computers and smartphones. Participants download the software, and when their computer or phone is inactive, it runs calculations to predict how a compound will interact with the virus in the lab. Researchers are also looking at repurposing existing drugs as Zika treatments. Chloroquine—which both prevents and treats malaria—has successfully protected against Zika virus in vitro. A team at Katholieke Universiteit Leuven has identified an experimental treatment for hepatitis C that delayed the manifestation of Zika-related symptoms in mice. And scientists at the University of California, San Francisco reported that the antibiotic azithromycin—which has long been used in pregnant women—blocked the virus from multiplying in petri dishes. Diagnostics As of March, more than 30 diagnostics for the virus were under development, and the FDA has sanctioned the use of five tests—four that detect current infection and one to assess previous exposure—under its Emergency Use Authorization program. However, rapid, point-of-care diagnostics are desperately needed. Eighty percent of cases are asymptomatic, and initial symptoms—fever, rash, joint pain—are nonspecific. Thus, early and accurate diagnosis is critical to ensure appropriate treatment. A team of Harvard University and Massachusetts Institute of Technology researchers have designed a paper-based test that can diagnose cases within a few hours. The device is appropriate for low-resource settings: it’s cheap, it can be stored or shipped at room temperature, and the results are easy to interpret. The tool contains miniscule sensors that change color in the presence of a specific genetic sequence. To ensure accurate detection of the virus, the team developed sensors that can detect 24 different genetic sequences found in the Zika genome. The device has been tested using samples from infected monkeys and has proven to be effective at detecting even low quantities of the virus. Although the results are easy to read—a positive sample turns the strip purple—the team has also created a simple electronic reader that determines the quantity of the virus in the sample. Vector Control As vaccines, drugs, and diagnostics against the virus inch their way through the R&D pipeline, health officials are ramping up vector control efforts against the Aedes aegypti mosquito. New techniques are also underway, and the FDA is currently accepting public comment on a proposal to expand testing of genetically engineered mosquitoes. The mosquitoes mate with the local population, resulting in offspring that die before reaching adulthood and are consequently not able to spread diseases. A trial of the mosquitoes in Brazil led to an 82 percent decrease in the Aedes aegypti population in just nine months. Scientists are using innocuous bacteria and fungi to combat the spread of Zika. Male mosquitoes infected with the Wolbachia bacteria do not produce viable offspring, and tests across the United States have reduced the population of the closely related Aedes albopictus mosquito by an estimated 70 percent. Meanwhile, the Metarhizium brunneum fungus is used as a natural pesticide, killing mosquito larvae. Meanwhile, in North Hempstead, New York, bats have been enlisted in the fight against Zika. The city is building and hanging bat houses in parks to attract the animals, as they can eat more than 1,000 mosquitoes in an hour.

The House Energy & Commerce Committee recently passed an amendment—attached to an unrelated bill—that would add requirements for eligibility to the Tropical Disease Priority Review Voucher (PRV) program at the US Food and Drug Administration (FDA). The PRV program, established by Congress in 2007, is intended to incentivize research and development (R&D) for drugs for which there is a critical need but a limited market opportunity. Under the program, the regulatory sponsor of an approved drug for a tropical or rare pediatric disease is awarded a voucher which expedites FDA review of a future product by four months. These vouchers enable companies to enter the market sooner, and several have been sold between companies for up to US$350 million. Of the three vouchers that have been awarded for tropical disease drugs, two were awarded to companies that weren’t actually involved in the drug’s development—they had merely acquired rights to the drug—and in one case, the drug was already approved by other regulatory authorities and available in 80 countries. The amendment, introduced by Congressman G.K. Butterfield (D-NC), would require the regulatory sponsor to demonstrate the need for the product (i.e., the global burden of the disease and demand for the product) and elucidate their plan to ensure access to the product. Vienna-based researchers have developed a vaccine against Toxic Shock Syndrome (TSS), a rare, life-threatening condition resulting from an extreme immune system response to a Staphylococcus infection. TSS is associated with the use of super absorbent tampons, and an estimated half of cases occur in menstruating women. In a phase 1 clinical trial, the vaccine candidate—which contains a detoxified strain of Staphylococcus—proved to be safe and successfully prompted an immune response. The vaccine will next be tested in a larger, phase 2 trial. The team anticipates the vaccine will last for five years and will be used to protect individuals with a compromised immune system who are at greater risk for TSS. Nature took an in-depth look at drug repositioning, in which a medicine developed to treat one disease or condition is used to treat another. Drug repositioning is not a new concept; leading drugs against HIV and AIDS and erectile dysfunction were once intended to treat cancer and angina, respectively. However, the practice is becoming more common. Since 2011, the number of journal articles published on repurposed drugs has increased sixfold to an average of 30 per month and each year three to four new companies focused solely on the practice are established. Generic medicines are a common target, however, there are also many drugs that have passed phase 1 or clinical trials, proving to be safe for use in humans, but that did not have the intended effect. This approach makes drug development cheaper and faster, as phase 1 trials can often be skipped. Repositioning a drug costs $300 million and takes 6.5 years, compared to $2 to 3 billion and 13 to 15 years when starting from scratch. However, phase 1 trials may still be needed if the drug needs to be delivered in a different way or if a different dose is needed. Additionally, many pharmaceutical companies have massive, untapped compound libraries and new technology and software have made it easier to discover ways in which distinct conditions manifest similarly on a molecular level, which allows them to better identify promising compounds to screen for a given condition or disease.

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.