Breakthroughs Blog: NIH

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.

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. An experimental oral antiviral drug showed promise as a potential treatment for COVID-19 after demonstrating an ability to prevent the virus from replicating, according to study results from the National Institutes of Health (NIH). The drug, TEMPOL, was tested in an experiment of cell cultures with live viruses and was able to impair an enzyme the virus needs to make copies of itself inside human cells, which could limit the severity of the disease. An oral drug to prevent virus replication would be an important tool, as additional effective and accessible COVID-19 treatments are still needed, according to the NIH statement. NIH researchers said they plan to conduct additional preliminary studies and will seek opportunities to evaluate the drug in a clinical study.The World Health Organization (WHO) approved the Sinovac-CoronaVac COVID-19 vaccine for emergency use on Tuesday after evaluating its safety, efficacy, and quality. Other COVID-19 vaccines that have been authorized by WHO include those developed by Sinopharm, Pfizer, Moderna, Johnson & Johnson, and AstraZeneca. The emergency use paves the way for countries around the world to approve and import the vaccine for distribution quickly, according to the WHO press release, in addition to being a prerequisite for use by the COVAX global vaccine-sharing facility. WHO also noted that the easy storage requirements of the vaccine make it suitable for use in low-resource settings.The COVAX advance market commitment (AMC) initiative raised US$2.4 billion to fund COVID-19 vaccines for low- and middle-income countries, in addition to 54 million vaccine donations, during a COVAX AMC virtual summit on Wednesday. This brings the total pledged to the COVAX AMC to $9.6 billion. The summit, hosted by the government of Japan and Gavi, the Vaccine Alliance, brought in donations from nearly 40 governments, the private sector, and foundations that will be used to secure 1.8 billion doses of COVID-19 vaccines for AMC-participating countries. The vaccines will be delivered in 2021 and early 2022 and will cover close to 30 percent of the adult population against COVID-19 in the 91 participating countries.