Breakthroughs Blog: NTDs

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.Last week, IAVI and Moderna announced that the first doses have been administered in a clinical trial of experimental HIV vaccine antigens delivered through mRNA technology. The phase 1 clinical trial, IAVI G002, is testing the hypothesis that administration of priming and boosting HIV immunogens delivered via mRNA technology can induce specific classes of B-cell responses and guide their early maturation toward broadly neutralizing antibody (bnAb) development. Inducing bnAbs via B-cells is widely acknowledged as a goal of HIV vaccination. The immunogens being tested were developed by scientific teams at IAVI and Scripps Research and will be delivered with Moderna’s mRNA technology.Global funding for poverty-related and neglected diseases, such as HIV/AIDS, tuberculosis, and malaria, remained virtually unchanged in 2020 at US$3.937 billion, according to the 14th annual G-FINDER report released by Policy Cures Research. The report—a comprehensive analysis of global investment of research and development for poverty-related and neglected diseases—showed a small decrease of $172 million, or 4 percent, in funding from 2019 to 2020, yet 2020 was still the third highest funding level for neglected diseases ever captured by G-FINDER data. The report identified other trends and insights, including the continued stagnation of funding for neglected tropical diseases, an increase in philanthropic funding and investment in platform technologies, and disruptions in clinical trials due to the COVID-19 pandemic.The cancer drug pembrolizumab can flush HIV out of its hiding spot in immune cells, which could help eliminate the virus in its latent stage, according to a new study published Wednesday. Currently, antiretroviral therapy—the standard treatment for HIV—can remove any trace of the virus from the blood, but a hidden reservoir of HIV persists in patients who are in treatment, meaning patients are never truly cured and must be on HIV drugs for the rest of their lives. The new study examined 32 patients that had both cancer and HIV and found that pembrolizumab, which revives the immune system and encourages it to attack tumors, also helps the immune system locate the last traces of HIV and disrupts the virus’ ability to hide. While these findings present an early proof of concept, researchers plan to continue additional studies to assess the drug’s impact at different dosing levels in HIV-positive patients without cancer.

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. Moderna is launching human trials for two new HIV vaccines based on the mRNA technology used in its COVID-19 vaccine, the company announced last week. The phase 1 trial will recruit 56 participants between the ages of 18 and 50 to assess the vaccines’ safety and ability to generate a broad range of neutralizing antibodies against HIV. The two vaccine candidates, mRNA-1644 and mRNA-1574, are designed to combat HIV by inducing broadly neutralizing antibodies to levels not previously obtained by other shots. The antibodies can then target multiple variants of HIV and neutralize stable parts of the virus that won’t change as much as it mutates. The study, expected to run until May 2023, is a first step in a long, complex process, according to researchers.Researchers have discovered a series of drug compounds that are highly effective against the three main species of parasitic worms that cause human schistosomiasis, according to new research published in PLOS Neglected Tropical Diseases. Currently, the only treatment for schistosomiasis is praziquantel, which is effective at a high dose against adult worms, but less so against juvenile worms, requiring repeat treatment. The new research involved screening more than 300,000 compounds to evaluate their ability to kill the worms, compared against praziquantel. The researchers identified a series of promising new drug candidates that appeared safe and highly effective against adult and juvenile worms—in a single dose around 10 times smaller than required for praziquantel. The drugs are now being explored by Merck Global Health Institute as a potential treatment for schistosomiasis.In phase 3 trial results, AstraZeneca’s COVID-19 antibody treatment, AZD7442, significantly reduced the risk of developing COVID-19 symptoms. The drug, a combination of two long-acting antibodies, reduced the risk of developing symptoms by 77 percent when given to patients who had not been exposed to COVID-19. No participants who were given the treatment developed a severe form of the disease. The monoclonal antibodies used in AZD7442, which mimic the body's natural immune response, were modified to be more long-lasting, potentially affording up to 12 months of protection. The drug could be particularly useful as a preventative treatment in patients for whom vaccines might be less effective, including immunocompromised individuals, AstraZeneca said in its statement. The company plans to submit the phase 3 results to a peer-reviewed journal and file for regulatory approval of the drug.

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.Solidarity, a global clinical trial led by the World Health Organization, will resume its efforts, testing three new treatments among hospitalized COVID-19 patients: artesunate, an antimalaria; infliximab, an antibody used to treat autoimmune disease; and imatinib, a cancer drug. The original Solidarity trial, which took place across dozens of countries simultaneously in 2020, found that none of the four treatments it tested showed benefit. While the original trial included antivirals, this new phase will focus on drugs that target the body’s immune response, rather than the virus itself, given the two drugs that have shown success in reducing mortality in hospitalized patients, dexamethasone and tocilizumbab, work by dampening patients’ immune reactions. Medicines have shipped to Finland as the first country to begin the trial with 40 more countries in the process of seeking ethical and regulatory approvals to join.Use of the monoclonal antibody therapy REGEN-COV reduced the risk of developing symptomatic COVID-19 infection by 81 percent in those exposed to an infected patient, according to a study published last week in the New England Journal of Medicine. The study, which included individuals over 12 who had a household member test positive within the prior 96 hours, found that by day 28, 1.5 percent of participants who received the therapy developed symptomatic infection compared to 7.8 percent who received the placebo. When including asymptomatic infections, risk reduction from the treatment was 66.4 percent. The study also found that patients who did become infected after receiving the therapy were more likely to have milder disease. These findings were used to support a decision late last month by the US Food and Drug Administration (FDA) to expand emergency use authorization for REGEN-COV to be used as a post-exposure prophylaxis among high-risk populations.Valneva shared positive results last week from the phase 3 trial of its single-dose vaccine against chikungunya, which found that 98.5 percent of participants saw protective antibody concentrations 28 days after receiving the shot. This protection rate exceeds the 70 percent threshold set by the FDA. The trial also found that the VLA1553 vaccine was generally well-tolerated and induced a high immune response among elderly trial participants. The trial will continue with outcomes evaluated until month six. VLA153 is currently the only chikungunya vaccine in phase 3 trials that targets long-term protection from a single-dose, according to its developer. The company signed an agreement earlier this year with the Instituto Butantan in Brazil for development, manufacturing, and marketing, with the goal of making the product more accessible in low- and middle-income countries.

“We might be tired of COVID-19, but it is not tired of us.” With those words punctuating his opening remarks, World Health Organization (WHO) Director-General Dr. Tedros Adhanom Ghebreyesus reminded World Health Assembly (WHA) participants that the ongoing pandemic continues to dominate both our lives and the agenda in multilateral fora. This year’s virtual assembly tried to continue to galvanize the global community around a coordinated response to the pandemic and reassert the importance of other key global health priorities. While this virtual assembly did not provide the same opportunities as years past to engage with stakeholders, GHTC tracked the proceedings and worked with partners to weigh in on key agenda items. Here are our top takeaways from this year’s forum:WHO and member states remain focused on pandemic response, health emergencies governanceWith the ongoing pandemic continuing to dominate the attention of the world, global coordination to address COVID-19 was a clear priority for WHO during the assembly. Delegates debated the challenges and gaps in the ongoing response efforts, as well as preparedness and response mechanisms for future health emergencies. The assembly also approved a resolution to bolster WHO’s work and strengthen countries’ preparedness capacities; while the resolution primarily focuses on health system strengthening, the International Health Regulations, and governance, it does include a provision that calls on member states “to facilitate investment in strong national research agendas and adequate infrastructures for research and development in support of new measures to counteract the impact of health emergencies, including non-pharmaceutical interventions.” The debate between member states over the resolution felt like a precursor for the more far-reaching reform proposals that may be in the offing next year, following the completion of multiple reviews over pandemic response that are now underway. Those reviews are looking at countries’ and WHO’s pandemic performance, WHO’s health emergencies program, and the International Health Regulations system itself. There appeared to be a slowly emerging political consensus shaping up around initiatives being advanced by both Germany and France to significantly strengthen the hand of WHO in terms of its emergencies powers to obtain data from member states and take action. Unfortunately, the proposals currently don’t formally integrate research and development (R&D) into their frameworks. WHO develops Immunization Agenda 2030  Member states expressed broad support during the assembly for the Immunization Agenda 2030, which outlines research and innovation as one of its seven strategic priorities, highlighting the need for “continued research into new and improved vaccines, technologies and vaccine manufacturing platforms, as well as innovations in immunization service delivery and program management.”Germany noted that the current strategy does not factor in the impact of COVID-19 on current immunization priorities and programs and that an additional evaluation to integrate pandemic response efforts will be necessary to adequately reflect the shifting landscape.WHO TB research and innovation strategy moves forwardThis year, WHO unveiled their new Global Strategy for Tuberculosis Research and Innovation, drawing on consultation with scientists, national tuberculosis (TB) program managers, and other officials from within and beyond ministries of health, including ministries of science and technology, representatives of civil society and affected communities, research funding institutions, and other TB research and innovation stakeholders. A resolution on this new strategy was passed by member states via silence procedure in the summer and formally adopted during the assembly.The strategy outlines four major areas for action: 1) creating an enabling environment for TB research and innovation; 2) increasing financial investments in TB research and innovation; 3) promoting and improving approaches to data sharing; and 4) promoting equitable access to the benefits of research and innovation. “This global strategy will guide member states and other relevant stakeholders in translating political commitments on TB research and innovation into concrete action backed by investment, as an integral part of efforts to end TB,” said Dr. Tereza Kasaeva, director of WHO’s Global TB Program. The WHO strategy also promotes the sharing of data arising from publicly funded research, with the ultimate goal of ensuring that the public benefits from public investments in science. The resolution also calls for WHO to provide technical and strategic assistance to member states, urges countries to strengthen efforts for TB research and innovation as a complement to broader cooperation to tackle antimicrobial resistance at all levels, and pushes for increased coordination across United Nations agencies and greater collaboration with the private sector.While the strategy is a welcome development, further investment for TB research must follow from member states. Global leaders must close the US$1.3 billion funding gap for TB R&D annually if the 2030 targets are to be achieved. WHA adopts new road map for neglected tropical diseasesWhile member states did not spend much time debating the topic, they did adopt a new road map on tackling neglected tropical diseases (NTDs) at the assembly. The NTD road map sets global targets and milestones to prevent, control, eliminate, and eradicate 20 NTD groups.One of the key components of the road map is a shift away from single-disease vertical programs to integrated approaches, which promote improved coordination and collaboration. Another distinct feature is to drive greater ownership by national and local governments, including communities. The overarching 2030 global targets include a 90 percent reduction in the number of people requiring treatment for NTDs and a call to eradicate dracunculiasis—also known as Guinea-worm disease—and the chronic skin disease yaws, which affects mainly children under 15 years old.Research and innovation will be a critical component to ensure that these targets are met, and several member states called for greater investment for new tools to combat these diseases.Civil society engagement with WHO remains limited Civil society engagement with WHO continues to be a challenging process, and after several disappointing meetings this year, this month’s assembly was no different. The often hectic and oblique communication, or lack thereof, on how civil society organizations (CSOs) could meaningfully participate in these meetings heading into the assembly was yet another sign that the trend line on productive collaboration between WHO and CSOs is heading in the wrong direction.CSOs were also prohibited from delivering statements on certain agenda items, and like member states, they were forced to consolidate a number of agenda items into a single statement as WHO pulled together several topics into one session, creating a disjointed dialogue in which not all issues received adequate airtime.Moving forward, WHO needs to provide new avenues for CSO input around these fora, whether through separate listening sessions, online consultations, or other mechanisms that allow civil society to bring its expertise to bear and provide technical feedback to various processes.This year’s assembly felt largely more ceremonial than substantive at times, given the lack of debate on many agenda items and WHO speeding through the list of topics. The pandemic will continue to be a major focus in 2021 for WHO and member states, but other health areas that have been neglected through underinvestment on the WHA73 agenda must also re-emerge as key priorities.