News

Even as Congress grapples with the White House on how to fund an emergency response to fight Zika virus, a new report warns that overall underfunding for development of lifesaving tools against neglected global diseases is putting the United States and the world at risk, and that emergency funding can’t be allowed to substitute for sustained US investment in research and development (R&D) of global health technologies. “Current levels of US global health R&D financing do not match the scale of health challenges the world faces,” said Erin Will Morton, director of the Global Health Technologies Coalition (GHTC)—27 nonprofit groups focused on accelerating the creation of new drugs, vaccines, diagnostics, and other health tools. “Political inaction in Washington could undermine two decades of landmark gains in global health and leave the world unprepared and unprotected against emerging health problems like Zika virus infection or antimicrobial resistance.” The GHTC report, Achieving a bold vision for global health: Policy solutions to advance global health R&D, was released today at a Capitol Hill briefing. In it, GHTC urges Congress and the Administration to recognize the United States’ crucial role in accelerating R&D that both saves lives around the world and protects the health of Americans at home. The report urges Congress to provide robust and sustained public financing for US agencies engaged in global health R&D, from the US Department of State and Department of Defense to the US Agency for International Development, National Institutes of Health, Centers for Disease Control, and Food and Drug Administration (FDA). It also calls for those agencies to then set a percentage of program budgets to be directed to global health R&D and for greater cross-agency coordination to accelerate health product development. “The Ebola and Zika virus outbreaks have exposed the perils of waiting for an emergency to trigger investment in R&D for neglected diseases. Sustained, predictable funding is not only more cost-effective, it’s a down payment to save lives from the diseases we’ll face tomorrow,” said Morton. A recent study that examined the risk of infectious disease outbreaks projected that large-scale global disease pandemics could cost the global economy more than US$60 billion a year, while investing in the interventions needed to protect against these outbreaks, including R&D, would cost only a fraction of that—$4.5 billion—each year. The GHTC report documents how past US support has led to breakthrough health solutions, like the first blood test for HIV/AIDS, a vaccine to prevent meningitis A in Africa, and new diagnostic tests to target drug resistant tuberculosis (TB), which have contributed significantly to major milestones in global health—since 1990, there has been a 53 percent drop in childhood deaths and a 45 percent decrease in maternal deaths. US investment have also helped nurture a growing global pipeline which contains nearly 500 promising tools under development for neglected global diseases, including: For malaria, new drug candidates in the pipeline; second-generation vaccines, and a new class of insecticides; For TB, shorter treatments for drug-resistant strains, easier-to-use, more rapid diagnostic tests, and efforts underway to develop a new vaccine; For Ebola, new vaccine and drug candidates moving through clinical trials; For drug-resistant superbugs, an entire new class of antibiotics; For HIV/AIDS, a new microbicide ring that has advanced through clinical trials and new hopes for a vaccine; and For neglected tropical diseases such as sleeping sickness, visceral leishmaniasis and Chagas disease, new drug cures and vaccines. GHTC credits much of this progress to the catalyzing effect from the near-doubling of US funding for global health R&D between 2000 and 2010. Since peaking in 2009, however, funding has been largely stagnant or declining. With Ebola emergency funding removed, US investments in neglected disease R&D in 2014 actually fell 2 percent from the year before and fell nearly 13 percent, or $221 million, from the 2009 peak. Despite uncertain year-over-year funding from the United States, the report says, developers around the world have contributed to a global health R&D pipeline today with nearly 500 products, up from 365 in 2012. The United States is the lead funder of this R&D, contributing around 70 percent of public investment and 45 percent of all global investment, including private and philanthropic funding. More specifically, the United States is the lead funder of R&D for 26 of the 30 most neglected diseases. “It is critical not to pull back US investments now and put this arc of progress at risk,” said Morton. “As promising global health products move from laboratory testing through clinical trials, costs escalate. So with great promise and success also comes a more pronounced need for funding to see these products to the finish line.” The GHTC report offers an example of cuts in US funding for Ebola R&D in 2012 that permanently stalled development of a promising vaccine, leaving the world empty-handed when an epidemic flared in West Africa. Policymakers could once again stall Ebola R&D if they redirect emergency funds allocated for Ebola R&D to fight Zika before we’ve completed development of Ebola diagnostics, vaccines, and other tools to curb future outbreaks. “We're missing a generation of biomedical interventions against neglected and emerging infections, and it's becoming increasingly clear that to solve this problem we'll need new partnerships and new strategic plans,” said Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, president of the Sabin Vaccine Institute, and a US Science Envoy. “The partnerships must include industry, developing country manufacturers, and nonprofit product development partnerships, with increasing financial and strategic support from the G20 nations, including the US government.” Recognizing that many of the diseases in question are ones of poverty, the GHTC report not only calls for robust public investment in global health R&D, but also suggests adoption of policies to incentivize the private sector to act in the absence of viable commercial markets. For example, prizes, small business innovation awards, priority review vouchers, advance market commitments, and tax credits could help leverage US investments. New financing mechanisms like social impact bonds or pooled funds could attract diverse and non-traditional funding partners. Investing in strengthening the R&D sector of fast-developing countries so they can address their own health challenges could also lessen US share of funding over time. Right now, however, the GHTC report insists the US cannot fall behind on its investments. Working together to get to the finish line faster Beyond funding, the report’s second goal is to direct greater cooperation and coordination across US agencies, which could close gaps and accelerate development of drugs, vaccines, diagnostics, and other tools. To achieve such coordination, the report recommends that Congress establish a whole-of-government R&D strategy, which could include a designated coordinator appointed to oversee it. It also calls for existing cross-government global health initiatives like the Global Health Security Agenda (GHSA) to adopt R&D as a core goal in dealing with future health crises. The third and final US goal recommended by the report is to deploy US expertise and resources to strengthen regulatory pathways to help get global health products into the hands of the people who need them more quickly. Regulatory capacity is often weak in the countries where new drugs, vaccines, and devices are meant to be deployed. The report recommends that Congress direct the FDA to establish a mechanism to offer a formal scientific opinion on medical products intended for markets outside the US, which would give authorities in countries lacking resources the trusted scientific guidance needed to make regulatory decisions. It also calls for greater support for programs to strengthen regulatory capacity in low- and middle-income countries and harmonize regulatory requirements. “When the US government and R&D sector strategically unleash their ingenuity and resources, there is no global health goal out of our reach,” said the GHTC’s Morton.

GHTC member the Drugs for Neglected Diseases initiative will test an affordable hepatitis C regimen in Malaysia and Thailand, with a guarantee from generic drug manufacturer Pharco Pharmaceuticals that, if successful, the product will be priced at no more than US$294 for the entire regimen. The regimen combines the registered drug sofosbuvir with the candidate ravidasvir, a promising treatment that cured up to 100 percent of patients with Hepatitis C genotype 4—the most common strain of the virus in the Middle East and Africa—in a phase 3 clinical trial in Egypt. The phase 2 and 3 trials in Malaysia and Thailand will test the regimen among 1,000 patients with different genotypes and the trial will be open to patients with varying levels of liver damage and those co-infected with HIV and AIDS. PATH announced last week that two new rapid diagnostics for onchocerciasis (river blindness) and lymphatic filariasis (LF) are now commercially available. Onchocerciasis and LF are neglected tropical diseases, caused by parasitic worms, and spread by blackflies and mosquitoes, respectively. Onchocerciasis primarily affects the skin and eyes, resulting in itching, skin nodules, and blindness, while LF damages the lymphatic system resulting in physical disfigurement and disability. The tests were developed by PATH in partnership with the US National Institutes of Health and Centers for Disease Control and Prevention and will be commercialized by Standard Diagnostics/Alere moving forward. The new tools include a diagnostic for LF and another that tests for both diseases simultaneously. Both provide results in just 30 minutes and can be stored at temperatures ranging from 1 to 40°C (34 to 104°F). These tools offer significant improvements over existing diagnostics for LF and onchocerciasis. Previously, diagnosing LF required health workers to draw blood at night, when the parasites are active and consequently detectable, while onchocerciasis tests relied on a skin snip—the removal of inflamed skin. The tests will be invaluable for surveillance, control, and elimination programs. Researchers from Canada and Mexico are using old tires and milk to reduce the population of Aedes aegypti mosquitoes, which carry the dengue, chikungunya, yellow fever, and Zika viruses. The device, known as an Ovillanta, is comprised of two 50-cm (20-in) sections of old tires—in which A. aegypti mosquitoes often breed—that are stacked to form a mouth-like shape. The Ovillanta is then filled with milk and a piece of wood or paper that floats like a raft. A. aegypti mosquitoes secrete a hormone when they lay eggs, which other mosquitoes use to identify ideal breeding spots. This hormone is initially added to the milk in the Ovantilla, and the mosquitoes are drawn to it, laying their eggs on the floating wood/paper, which are then collected and destroyed. The Ovillanta is an adaptation of the ovitrap, which uses a bucket and water rather than old tires and milk. The team, funded by Grand Challenges Canada, has been testing the Ovillanta in Sayaxché, Guatemala, and over ten months, the Ovillanta has proven seven times more effective than standard ovitraps. The team will next test the device throughout the region and have shared the design online so that anyone can create one for personal use.

Aedes aegypti mosquitoes which carry Zika. Photo: Dean Calma/IAEAApril showers bring standing pools of water, the onset of mosquito season, and a new wariness of getting bitten. In 1999, we were caught off guard when the West Nile virus first appeared in North America. In 2010, an outbreak of dengue fever spread locally in Florida after an absence of 60 years. In 2014, chikungunya first arrived in the United States after travelling breathtakingly fast through the Western hemisphere. Now, in 2016, Zika virus is the latest mosquito-borne disease to threaten Americans. Yet our collective national response continues to be one of short-term planning rather than long-term preparedness.Since Zika virus arrived in the Americas in May 2015, there has been an alarming spike in reports of birth defects such as microcephaly, particularly in Brazil. Zika infection has also been linked to adverse pregnancy outcomes and Guillain-Barré syndrome—a temporary paralysis that can prove deadly. The World Health Organization has declared Zika a Public Health Emergency.The virus has now spread to 26 countries, including 312 travel-associated cases in the United States. So far, mosquitoes in the United States haven’t infected anyone, but the Centers for Disease Control and Prevention (CDC) just issued a revised map that shows the mosquitoes that carry this virus and others can be found across the Southern tier of the United States all the way up to southern New England on the East Coast.Faced with this chilling situation, we don’t have ready the tools we need to fight Zika. Just like with Ebola, crucial tools did not exist or were still under development when the outbreak began. R&D is urgently needed to understand the Zika virus and its associated health conditions, and develop new diagnostics, vaccines, or other treatments to combat it. A pregnant woman in El Salvador receives an ultrasound as part of the country's response to the Zika outbreak. Photo: Office of the President of El Salvador Today, the Band-aid approach of emergency funding is the only option available to mitigate the crisis. We applaud President Obama’s call for accelerated research efforts, and the need to inform Americans about how to protect themselves, which the CDC has been quick to do. The National Institute of Allergy and Infectious Diseases, led by Dr. Anthony Fauci, has also called for a “full court press” on research.This requires increased funding for those searching for ways to stop this virus. Diverting resources from the Ebola response, however, is short-sighted. Those efforts are just beginning to show the promise of new diagnostics, advanced therapeutics, and more resilient health systems in Ebola-affected countries. Redirecting funding before the job is finished is dangerous, and will most certainly leave the United States and the world unprepared for the next Ebola outbreak.The fact remains that this long-standing patchwork approach to global health R&D funding only degrades our ability to respond to the guaranteed next global health crisis. With more than 500 mosquito-borne diseases across this globally interconnected world, the question is not if but when we see another virus or disease.Just as we need primed and ready firehouses and firefighters, we need a primed and ready research infrastructure. That requires a prioritized agenda and sufficient funding. America’s “firehouses and firefighters” are the National Institutes of Health, CDC, President’s Malaria Initiative and the Army and Navy’s tropical infectious disease programs.Global health means everyone’s health. It’s time US policymakers stop funding by crisis and commit to sustainable, long-term investment in global health R&D so the most effective health solutions are available when they are needed.Stephen Higgs, PhD, FRES, FASTMH is the president of the American Society of Tropical Medicine and Hygiene and a professor at Kansas State University. Erin Will Morton, MA is director of the Global Health Technologies Coalition, a group more than 25 nonprofits that work to save and improve lives by encouraging the research and development of essential health technologies.