Breakthroughs Blog: NIH

President Joe Biden has made clear that addressing climate change is a top priority for his administration. Since January, the president has issued executive actions in pursuit of tackling the climate crisis; opened a new federal office for climate change, health, and equity; and convened two meetings of the Major Economies Forum on Energy and Climate, one of which was part of a larger leaders summit intended to rally world leaders to strengthen climate ambition in the lead-up to the 26th United Nations Climate Change Conference of the Parties (COP26) in early November, during which countries hope to negotiate shared climate commitments.Amid these ongoing and vital conversations, GHTC is taking stock of how global health and climate are intertwined and how innovation can address these twin issues and mitigate the impact of climate change on human health. As the Unites States prepares to engage in COP26, we hope to see continued commitments and concrete actions to combat the climate crisis, including climate-related global health challenges.Climate-related global health risksClimate and global health are inextricably linked: Climate change could put billions more people worldwide at risk of vector-borne and zoonotic diseases like malaria and dengue. Changing temperatures have been described as a “threat multiplier” of antimicrobial resistance, due to warm conditions being more favorable for bacterial reproduction. The climate crisis exacerbates food instability and malnutrition as a result of droughts and other extreme weather events—circumstances which also prove opportune for disease outbreaks. The threat of a “Disease X” outbreak occurring, and spreading globally, is greater than ever before due to deforestation and other climate-related risk factors.These risks will not be felt equally around the world. Children are among the most vulnerable—and will be exposed for the longest—to health risks resulting from climate change, given their physical and cognitive immaturity. Health effects are also expected to be worse for people who are older, have preexisting medical conditions, or are living in poverty or in low- and middle-income countries. These populations are less able to insulate themselves through technology, housing, social networks, health services, and other infrastructure. Food insecurity is likely to particularly affect Indigenous communities, many of which rely on local food sources, such as fish. Women and girls, too, are often underprioritized in responses to climate-induced disasters, which can inhibit their agency and access to sexual and reproductive health services, from contraception to HIV prevention and treatment.Existing efforts by US agenciesThe US government is beginning to recognize and take on the interconnected fight against climate change and global health crises through programs at the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), and US Agency for International Development (USAID).For example, CDC’s Climate and Health Program assists states, cities, territories, and tribes in the United States with protecting human health from a changing climate by providing data, tools, and technical guidance to reduce vulnerability and increase resilience.NIH has launched a Working Group on Climate Change and Health aimed at addressing climate change and its health effects through research and innovation, and its National Institute of Environmental Health Services Climate Change and Human Health Program funds research aimed at understanding the health effects of climate change.USAID conducts a breadth of climate-related work, playing a crucial role in mitigating climate change and supporting resilience against its global impact—including by strengthening resilient food systems. USAID-supported programs have worked to develop and distribute disease-, heat-, and drought-tolerant seeds as well as nutrient-dense foods. For example, to support response to climate change–induced droughts and dry climates, USAID has invested in a public-private partnership to develop a variety of drought-tolerant maize, which was used by 6 million farmers in 2016 when the El Niño drought hit Southern and Eastern Africa.Looking ahead: What more should the US government do?In line with its expressed priorities, the US administration should continue to sustain and expand investment in climate change innovation—embracing a comprehensive agenda that recognizes the need to not only directly improve climate health, but also mitigate its impact on human health. While US health agencies have demonstrated some capacity to take on climate action for health, there is much more to be done.US agencies addressing climate change should consistently consider its ripple effect on global health and integrate a broad range of health-related climate innovation into their work—for instance, through emerging infectious disease surveillance, health and environmental systems capacity strengthening, or research to further understand both threats and the ways they interact.We will never achieve global health goals without also protecting our environment, and we won’t succeed in preventing the climate crisis’s worst impacts without bolstering investments in global health. GHTC looks forward to seeing continued commitment and global leadership from the US government to advance innovation to address these deeply intertwined challenges.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. In a small study, nine people who received lab-made monoclonal antibodies were deliberately exposed to mosquitoes carrying the parasite that causes malaria—and did not become infected. In comparison, five of six people in the untreated control group developed the disease. The monoclonal antibody works by binding to a small portion of the circumsporozoite protein that studs the surface of the sporelike stage of the Plasmodium falciparum organism. While the trial was too small to confirm efficacy of the antibodies as a preventive method, the study will act as a proof of principle and open a new avenue for malaria prevention. The research team is now developing a new monoclonal antibody that is two to three times as potent, which it intends to test next year in a clinical trial in Mali. A single injection of pre-exposure prophylaxis—or PrEP, used as an HIV prevention method—once every two months lowered HIV risk by 66 percent more than a daily pill, according to results from a three-year, real-world study. The study tested a single 600 milligram shot of cabotegravir, a long-acting antiretroviral cocktail, against Truvada, a daily oral antiretroviral drug regimen, among more than 4,500 patients. The difference in effectiveness was primarily a result of adherence, according to the research team—the PrEP shot guaranteed two months of protective medicine, while the pill regimen relies on maintaining a strict daily schedule. The bimonthly cabotegravir injection is currently under review by the US Food and Drug Administration, with a decision expected in late 2021 or early 2022.On Friday, Bharat Biotech’s intranasal COVID-19 vaccine received regulatory approval in India to begin phase 2/3 trials after the nasal spray was well-tolerated in a phase 1 trial of volunteers aged 18 to 60. The adenoviral intranasal vaccine was safe, immunogenic, and well-tolerated in the preclinical toxicity studies and was able to elicit high levels of neutralizing antibodies in animal studies. The vaccine, known as BBV154, is the first nasal spray COVID-19 vaccine to undergo human trials in India. Bharat Biotech’s injectable COVID-19 vaccine, Covaxin, is already authorized for emergency use in India after demonstrating 77.8 percent efficacy against symptomatic COVID-19 and 93.4 percent efficacy against severe illness during its phase 3 clinical trials.

The Biden administration has proposed a new, cutting-edge research entity that has the potential to benefit global health the way the Defense Advanced Research Projects Agency (DARPA)—the research agency behind the internet, GPS, and self-driving cars—benefited the rest of society. This proposal, the Advanced Research Projects Agency for Health (ARPA-H), could lead to transformative health innovations for neglected diseases and address gaps caused by market failures, ultimately bolstering global health research and development (R&D). What is ARPA-H? Initial proposals from the Biden administration and allies in Congress have described ARPA-H as a driver of scientific breakthroughs for innovations to prevent, detect, and treat diseases that will be housed within the National Institutes of Health (NIH). The idea for ARPA-H was originally conceived by the Suzanne Wright Foundation, a pancreatic cancer advocacy organization, which outlined a Health Advanced Research Projects Agency that would focus on overcoming market failures by de-risking investments from the private sector. Now that the proposal has been taken into the mainstream by the Biden administration and biomedical R&D champions like Representatives Diana DeGette (D-CO) and Fred Upton (R-MI), advocates hope this mandate of addressing market failures might also encompass global health issues including HIV/AIDS, malaria, tuberculosis, and neglected tropical diseases. The scope of research to be conducted under ARPA-H has not yet been set in stone, even though the president’s fiscal year 2022 (FY22) budget request lists as initial focus areas cancer, diabetes, and Alzheimer’s in its $6.5 billion request for the agency. NIH has organized listening sessions, including one for allergies, infectious diseases, and global health, to further discuss the potential research areas for ARPA-H.  To promote high-risk, high-reward research, ARPA-H will likely be modeled after DARPA, which has a flat and nimble organizational structure and a large budget with limited oversight. In contrast to NIH’s sometimes slow-moving peer review process and multiyear grants, DARPA utilizes program managers who make unilateral funding decisions based on research milestones achieved. If the agency is stood up, GHTC supports an ARPA-H funding framework that is similar to DARPA, as it could enable easy, flexible collaborations with product development partnerships—nonprofit partnerships that address public health goals.The Biden administration’s proposal to house ARPA-H within NIH has raised concerns among some advocates and skeptics that this could limit its flexibility and independence, two critical aspects of the ambitious high-risk, high-reward ARPA-H agenda. An additional concern is that placement within NIH could eventually limit growth of top-line funding available for other NIH institutes and centers, and the lack of clarity regarding the scope of focus areas for research has created hesitancy among congressional appropriators to fund the full $6.5 billion proposed. However, if ARPA-H is created with the flexibility and independence of DARPA, and its funding is additive so as not to diminish work on any other NIH program, the agency holds great promise for global health innovations. Global health potential With the right influence from advocates, ARPA-H has the potential to advance research that could benefit the lives of people living in impoverished and underprivileged communities worldwide. Poverty-related and neglected diseases (PRNDs) affecting these communities remain inadequately addressed by the market, as they offer little commercial incentive for the private sector to invest in developing medical products to diagnose, treat, or prevent them. The lessons of the COVID-19 pandemic highlight the need to address gaps in existing PRNDs as their impacts are exacerbated during health emergencies. With a focus on PRNDs, ARPA-H could make a substantial impact toward developing innovations to address the world’s most overlooked diseases.GHTC is not the only stakeholder that recognizes the global health potential for ARPA-H. During a Senate budget hearing for FY22 on NIH, Dr. Francis Collins, NIH’s director, said that one focus for ARPA-H could be the development of a universal vaccine that protects against the ten most common infectious diseases in a single shot. The opportunity for further influencing the scope and mission of ARPA-H remains open. Just recently, Representatives DeGette and Upton, lead sponsors of the landmark 21st Century Cures Act of 2016 who are now developing a follow-up bill, issued a request for information on the possible authorization of ARPA-H in their bill, with questions including, “To ensure it has the biggest impact, on what activities or areas should ARPA-H focus?” In response, GHTC submitted feedback advocating for a focus on PRNDs, including HIV/AIDS, tuberculosis, malaria, and neglected tropical diseases, as well as antimicrobial resistance, arguing that a focus on these areas of historic market failures holds the greatest potential for ARPA-H’s societal impact. ARPA-H could produce transformative health innovations in chronically underfunded areas. If the agency is authorized, GHTC and other advocates should encourage lawmakers to ensure R&D for PRNDs is prioritized. The innovations that result could yield additional advancements across the entire field of biomedical R&D, improving health for all.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email.University of Cambridge scientists have identified 200 existing drugs as possible candidates to repurpose against COVID-19 and validated two of them in early tests—the antimalarial therapy proguanil and rheumatoid arthritis medication sulfasalazine. In the study, both drugs safely inhibited the replication of SARS-CoV-2 in monkey and human cell lines. Both are well established and well tolerated for other human diseases and will likely be rapidly advanced into clinical trials to test whether they can prevent or treat COVID-19. The Cambridge research, which mapped a network of human proteins induced by SARS-CoV-2 infection, identified 476 key proteins most relevant in viral replication and screened approved drugs against those proteins, finding 200 drugs, 40 of which are already in COVID-19 clinical trials and another 30 of which have previously been proposed as potential candidates against the disease.A malaria vaccine candidate that pairs a shot of the live parasite that causes the disease with a dose of infection-fighting drugs showed promise in early clinical trials, researchers reported in Nature last week. The live parasite vaccine and drug combination showed 87.5 percent efficacy in a small group of healthy adult participants. The study, conducted at the National Institutes of Health, gave 44 healthy people in the United States three intravenous doses of the vaccine spaced about a month apart, followed by one of two antimalarial drugs—pyrimethamine or chloroquine—two or three days after the shot to weaken and eliminate the parasite. A phase 2 clinical trial of the vaccine is now underway in Mali, a malaria-endemic country.The CoronaVac COVID-19 vaccine appears to be safe and induce an antibody response among children and adolescents ages 3 to 17, according to phase 1/2 clinical trial data. The vaccine, manufactured by Sinovac, has recently been approved for emergency use in China for children over the age of 3. The trial results evaluated the vaccine among healthy children and adolescents in Zanhuang County, China, finding 96 percent of participants who received two doses of the vaccine developed antibodies against SARS-CoV-2. Most adverse reactions were mild or moderate, with pain at the injection site the most commonly reported symptom. Researchers noted that the number of participants was small and concentrated and recognized a need for larger studies in other regions, as well as for data evaluating long-term safety and immune responses.