Breakthroughs Blog: Malaria

2022 G-FINDER report highlights the inadequacy of global health R&D funding: GHTC offers key takeaways for the global health communityThe release of the 2022 G-FINDER report sheds light on current funding trends in global health research and development (R&D). Despite hard-won advocacy victories by GHTC and the global health advocacy community, neglected diseases are living up to their moniker from a funding standpoint, as global investment in HIV/AIDS, tuberculosis (TB), malaria, and neglected tropical diseases (NTDs) remains far below levels required to overcome these persistent and devastating health threats. The new report highlights several new and ongoing funding trends. GHTC has identified three findings of particular importance to the global health research community.Funding for NTDs dropped precipitously; funding shortfalls for HIV/AIDS, malaria, and TB persist.Funding for NTDs included within the G-FINDER scope decreased by 10 percent in 2021, falling to their lowest total since 2009. NTDs impact more than a billion people each year, disproportionately afflicting women and children. The reduction in funding is particularly alarming given that many of the targets set in the WHO roadmap on NTDs (2012-2020) have not been met. Outside of NTDs, funding for malaria saw a substantial 5.7 percent dip, HIV/AIDS investment experienced a modest uptick of 2.7 percent, and TB funding remained virtually flat, dipping less than a tenth of a percent. While these three diseases receive more resources than NTDs, their funding levels are significantly below that which is needed to overcome these health crises and reach global health and development targets, like the Sustainable Development Goals.Funding for Product Development Partnerships (PDPs) declined for the fourth consecutive year.PDPs are the leading engines of medical innovation for diseases that lack sufficient commercial market incentives. Thus, it is distressing to see that neglected disease R&D funding for PDPs fell by 18 percent in 2021, continuing a multiyear backslide. Current PDP funding sits 40 percent below its peak, which was 13 G-FINDER cycles ago. The most recent dip was driven by reduced investment from large donors like the Bill & Melinda Gates Foundation, the UK Foreign, Commonwealth & Development Office, and the US Agency for International Development (USAID). These findings also highlight the need to further diversify funding sources for PDPs, as well as global health R&D more broadly. Specifically on the US government funding front, PDP funding was not the only area in which USAID funding declined. Neglected disease R&D funding from the agency reached a record low, further highlighting the need for additional mechanisms within USAID to facilitate supporting medical innovations for unmet needs. During the virtual launch event for the report, keynote speaker Dr. Peter Hotez noted the vital role that US agencies like USAID and the US National Institutes for Health play in the global health R&D ecosystem.Funding for platform technologies and non-disease-specific investment is on the rise. For the seventh consecutive year, funding for non-disease specific (NDS) R&D increased, rising by 5.6 percent. Specifically, investment in platform technologies grew for the fourth consecutive year and now accounts for 22 percent of NDS funding. Much of the past year’s growth was buoyed by an increase in drug-related platform technologies, which historically received the smallest share of funding. This trend dovetails with a larger shift of investments toward drugs, as overall drug R&D funding eclipsed vaccine R&D funding for the first time in 2021.Overall, the global health advocacy community has made incredible strides in protecting and growing funding for global health innovation. This past year in the United States, GHTC helped support the passage of a global health research-friendly fiscal year 2023 omnibus package, which included significant funding increases across nearly every line relevant to global health R&D, as well as complimentary directives that will support global health R&D across several agencies. However, the challenges of competing global interests and tough funding environments are formidable, as shown by the G-FINDER report. This coming year presents a number of strong opportunities to elevate attention and support for resources for global health innovation, including United Nations High-Level Meetings on TB and universal health coverage. We urge leaders around the world to step up and invest in lifesaving global health R&D, and our advocacy community partners to continue to hold the world accountable for ensuring health and health equity for all. 

Next week, the World Health Organization’s (WHO’s) 152nd Executive Board (EB) meetings kick off in Geneva, with delegates and civil society representatives participating in person for the first time in two years. Recent months have seen a shift away from COVID-19 and an increased focus on long-term reforms to the broader global health architecture. While the dialogue around designing global frameworks and new mechanisms to address future health threats is vital, many of the discussions on poverty-related and neglected diseases are seemingly absent from this year’s discourse.  Here are the four issues to watch at this year’s meetings: Continued focus on global health security  2022 was a fruitful year for advancing two processes that will significantly influence the future of pandemic response. First, the intergovernmental negotiating body tasked with shepherding the Pandemic Accord process developed its first conceptual draft for the new framework. This comes following multiple public hearings, member state negotiations, and consultations on specific elements including equity, access and intellectual property, and antimicrobial resistance. Encouragingly, the document includes some strong research and development (R&D) focused language and recognizes R&D as an integral pillar of health preparedness. However, the current draft emphasizes downstream response measures such as manufacturing and registration, with less of a focus on early-stage research, clinical development, and even post-registration access and delivery of health tools. Additional focus on early-stage discovery research, clinical development, regulatory processes, and access and delivery of medical countermeasures is needed to ensure the type of true end-to-end approach critical to global health security. The second major global health security focused process has been centered around targeted amendments to the International Health Regulations. This policy discussion primarily focused on changes to provisions on trade and travel health certificates, as well as data-sharing and reporting requirements. Though perhaps less prominently discussed, disputes over intellectual property, in particular those centered on genetic sequence and pathogen sharing, remain major barriers to consensus. Both of these processes will be debated during EB, and we can expect a concerted effort to clearly delineate these processes and advance dialogues around defining the terminology and scope of both endeavors.  Limited progress on the implementation of the clinical trials resolution Last year, member states passed a resolution on clinical trials with the intent to build on lessons learned from the COVID-19 pandemic. The crisis drove a surge in funding for clinical research on COVID-19 tools, but we also saw many trials that were not large enough or that failed to employ consistent protocols and outcome measurements across geographies, making it difficult to pool and compare data to turn conclusions into medical practice. Among other matters, the resolution urged countries to better coordinate research, standardize protocols, improve reporting on trial registration and results, and work to increase clinical trial capacity globally, particularly in low- and middle-income countries—though none of these actions are binding. It also requested that WHO develop a global action plan to strengthen clinical trial practices to be presented for consideration at this year's assembly.EB will provide a chance to level set the current status of the implementation of the clinical trials resolution and figure out which elements of the framework could be improved. Previous discussions suggest that the current progress in implementing the resolution has been limited. During consultations held last fall, member states highlighted gaps in data on specific population groups and disease targets, as well as gender biases in data, which may result in these groups being precluded from access to needed interventions, as a point of inequity that must be addressed. The public consultation also noted the crucial importance of strengthened national regulatory authorities and national ethics committees, as well as increased international collaboration and coordination for efficient funding of agreed-upon priorities for multinational and multiregional trials, where appropriate.  The EB now has a chance to build on the progress and push WHO to follow through on their global action plan and for member states to support mechanisms like the WHO International Clinical Trial Registry Platform to push this agenda forward.  A new resolution on diagnostics could be passed New on the docket this year is a resolution that focuses on the development of—and access to— diagnostics. A recent Lancet report sounded alarm bells, highlighting that almost half of the global population has little or no access to diagnostics. The COVID-19 pandemic has clearly shown that a country’s diagnostic capacity is directly linked to its ability to respond to pandemics with appropriate public health measures and effective monitoring of emerging variants. Given the depth of the challenge, sustained access to quality, affordable diagnostics will require multi-decade prioritization, commitment, and investment.  This resolution is a good first step in acknowledging the need for more political will in addressing the diagnostics gap. Notably, it urges member states to develop a National Essential Diagnostics List, adapting the WHO Model List of essential in vitro diagnostics and the WHO List of Priority Medical Devices. The resolution further urges countries to invest in R&D, expanding manufacturing capacity for diagnostic medical devices and surveillance and strengthening international collaboration and assistance during epidemics and pandemics.  The resolution also calls on WHO to support member states to strengthen national and regional regulatory systems for diagnostic medical devices, collect data on the affordability and availability of essential diagnostic medical devices, and consider and support mechanisms for procurement that will enable access to high-quality, affordable diagnostic technologies for all member states. Some hurdles to approving this resolution remain, including outstanding disagreements on whether to include provisions pertaining to intellectual property and access, but there appears to be broad support from member states to get this resolution across the finish line in Geneva.  UHC back in the spotlight Universal health coverage (UHC) is also back in focus for this year’s EB, especially with September 2023 marking the halfway point of the timeline to reach the Sustainable Development Goals (SDGs) and leaders preparing for a United Nations High-Level Meeting on them at this year’s General Assembly. While some progress toward the SDGs has been made, the COVID-19 pandemic caused major disruptions in both health services and the development of health system capacities globally.  From a research perspective, a report by WHO ahead of EB highlighted that research and innovation continues to play a crucial role in UHC. Inequitable access to medical products is among the main causes of financial hardship in many lower- and middle-income countries. The report also notes how the recent World AIDS Day 2022 campaign highlighted the dangers of these inequalities, calling on global leaders and citizens to equalize access to essential HIV services, particularly for children and key populations, in order to end AIDS as a public health threat.  EB is a chance to hit reset on the UHC dialogue and for countries to reaffirm their commitment to the SDGs. It is also an opportunity to reassert that health system strengthening supports all health areas, including pandemic preparedness and poverty-related and neglected diseases. It is vital that leaders break down silos and take a more holistic approach to ensure progress toward advancing the global development agenda and 2030 targets. As discussions on global health architecture reforms advance, and new investments in pandemic preparedness are made, it is vital that global decision-makers ensure the benefits of these resources are also leveraged to benefit the fights against tuberculosis, HIV, malaria, and neglected tropical diseases. 

2022 has been a year of both formidable global health challenges and exciting innovations in research and development (R&D). In addition to the ongoing COVID-19 pandemic, the year saw alarming outbreaks of mpox (monkeypox) and Ebola. These crises further highlight the importance of building adequate capacity to prevent and respond to outbreaks and pandemics. Greater investment is urgently needed to ensure we have the global health technologies and R&D capacity to develop lifesaving, transformative innovations like the COVID-19 vaccines, and to address the resource and access gaps that exacerbate the worst effects of these outbreaks and diseases. With adequate investment and political will, breakthroughs are possible—and we have seen several this year.As the year comes to an end, GHTC reflects on a few of the global health innovation stories that shaped 2022.1. mRNA vaccine technology is being applied to existing and future pandemicsThe rapid development and dissemination of messenger RNA (mRNA) vaccines for COVID-19 has generated a wealth of data about the safety and efficacy of mRNA vaccine technology.   The Moderna and Pfizer/BioNTech mRNA COVID-19 vaccines have already saved millions of lives as new formulations continue to gain approval. Their success has also helped advance the clinical development of vaccines for other respiratory diseases including influenza and respiratory syncytial virus (RSV).Renewed interest and tremendous progress in the development of a universal flu vaccine can be connected to the rapid development of mRNA COVID-19 vaccines and an increased focus on pandemic preparedness. Recent results from an exciting trial investigating a universal mRNA vaccine for influenza showed that the vaccine reduced flu symptoms and deaths, although further testing in humans is needed to confirm its safety and efficacy.This year, we have seen exciting new uses of mRNA technology for a variety of infectious diseases—including those yet to surface. There has been either interest in or initiated clinical trials evaluating vaccines using mRNA technology for HIV, tuberculosis (TB), Nipah virus, malaria, and Ebola. Additionally, we have seen pandemic preparedness efforts harnessing mRNA technology take shape. This past year, Moderna announced an initiative to develop mRNA vaccines for emerging pathogens and the Coalition for Epidemic Preparedness Innovations announced an effort to build a mRNA vaccine library against Disease X (the next pathogen with epidemic or pandemic potential that has been yet to be identified).2. Africa continues to strengthen R&D capacitiesThis year has seen a series of accomplishments indicating the flourishing role of Africa in global health R&D efforts, particularly around pandemic preparedness. 2022 saw the decision to make the Africa Centres for Disease Control and Prevention a fully autonomous agency, giving it more authority to assess and respond to disease outbreaks on the continent.Additionally, in 2022, the South African Health Products Regulatory Authority was classified by the World Health Organization (WHO) as maturity level three (on the four-level scale), a step that recognizes the stability and reliability of the agency in ensuring the safety, quality, and effectiveness of vaccines. The South Africa mRNA hub, which was launched by WHO in 2021, despite challenges, has begun development of an mRNA vaccine for TB and is working on developing a local mRNA vaccine candidate for COVID-19.Universal Corporation Ltd, supported by Medicines for Malaria Venture and Unitaid, this year became the first African manufacturer to gain WHO prequalification of sulfadoxine-pyrimethamine, marketed as Wiwal, a malaria drug aimed at preventing malaria in pregnant individuals and infants.3. Urgency and awareness of antimicrobial resistance is on the riseAntimicrobial resistance (AMR) continues to grow as a global health security threat, and many new reports and studies this year have documented the alarming trend. A 2022 report from Global Research on Antimicrobial Resistance found that AMR has become a leading cause of death globally, with the most deaths directly linked to AMR in sub-Saharan Africa and South Asia. Another recent report from WHO echoed the severity and growing threat of AMR around the world.Two 2022 WHO reports aim to contribute to overall understanding of AMR and the need for investment in R&D of new tools to strengthen the global response to it. The first identifies, in the context of AMR, 61 bacterial vaccines in clinical development and 94 candidates in preclinical development, and the second, more recent report identifies priority fungal pathogens including critical pathogens like Cryptococcus neoformans, Candida auris, Aspergillus fumigatus and Candida albicans. Hopefully, the focus on and investment in new tools to address AMR continue into the next year.4. Beating back malaria with the rollout of RTS,S vaccine and additional malaria technologiesAfter last year’s approval of the RTS,S malaria vaccine, 2022 saw the beginning of the rollout of this groundbreaking technology. Malawi, Ghana, and Kenya initiated routine immunization programs that will hopefully play an important role in the global effort to eliminate malaria. This year, a University of Oxford research team also published promising results for a new malaria vaccine, R21. The developers say the vaccine can be produced for just a few dollars and that they expect it to be rolled out next year through a manufacturing deal for more than 100 million doses a year, in partnership with the Serum Institute of India.  A new “mosquito-grounding” insecticide, Chlorfenapyr, that causes mosquitos’ wings to spasm and wither could also bolster the fight against malaria, according to trial results published earlier this year. Insecticide-treated bednets have been central in efforts to reduce the spread of malaria, but rising insecticide resistance among mosquitos has hampered progress, and Chlorfenapyr is the first new insecticide to be deemed safe and effective in about 40 years.Finally, this year, Australian regulators approved a simple drug combination as an effective cure for children ages 2 to 16 with Plasmodium vivax malaria, adding a new tool in the battle against the disease and opening the door to approval in other countries. The drug—tafenoquine, developed by GlaxoSmithKline and the Medicines for Malaria Venture—is a single-dose treatment administered alongside traditional chloroquine treatment.Due in part to previous innovations in antimalaria tools, progress against malaria has largely held in recent years, despite disruption from the COVID-19 pandemic. These next generation tools will be key to accelerating progress over the coming years.5. Outbreaks of mpox trigger innovation in developing treatments and vaccinesRising cases of mpox in the first half of 2022 drove interest in an existing range of vaccines and treatments with the potential to offer protection against the outbreak. The mpox virus, which causes a usually mild infection, is closely related to the smallpox virus—and smallpox vaccines appear up to 85 percent effective in preventing mpox, according to WHO. The National Institute of Allergy and Infectious Diseases and the Democratic Republic of the Congo’s National Institute for Biomedical Research are co-leading a clinical trial evaluating the safety and efficacy of the antiviral drug, tecovirimat (TPOXX) in adults with monkeypox. SIGA Technologies, Inc.’s TPOXX is approved for the treatment of smallpox in the United States.Facing low supply of Jynneos, the only vaccine approved for use against monkeypox in the United States, the US National Institutes of Health launched a clinical trial to test an alternative vaccine administration method to stretch the limited supply. The dose-sparing method involves giving two doses, each one-fifth of a full dose and administered intradermally.While monkeypox cases have diminished, these trials will provide essential data about the safety and efficacy of tools to address the disease that has long been neglected before this year’s outbreaks in high-income countries like the United States and the United Kingdom.6. Sudan Ebola outbreak prompts clinical trial and calls attention to gaps in outbreak preparednessOne of the most distressing developments of 2022 was the outbreak of the rare Sudan strain of the ebolavirus in Uganda. The response, however, advanced innovative approaches and highlighted the need for increased preparedness in the future.Following the identification of the outbreak, WHO announced a clinical trial of three experimental vaccine candidates to address the outbreak. The vaccines tested in the trial include one produced by IAVI, one developed by the Sabin Vaccine Institute, and a third developed by the Jenner institute at the University of Oxford. While the trial is expected to begin shortly, the spread of the Sudan ebolavirus in Uganda has slowed dramatically, raising questions whether the trial could continue. It is clear that despite the incredible amount of effort from various cross-sector global partners to secure the vaccines, permissions, and funding for the trial, responses to such outbreaks need to occur even quicker, which can be accomplished by developing stockpiles of experimental vaccines and pre-agreed trial protocols.7. Pretomanid and the BPaL regimen honored at GHTC’s annual awardsGHTC presented the 2022 Innovating for Impact Partnership Award to TB Alliance for the development of pretomanid and the BPaL regimen—an innovative treatment for drug-resistant DR-TB. Pretomanid, the first TB drug developed by a nonprofit organization, is part of the three-drug “BPaL” regimen. This innovative new therapy reduces the time needed to treat DR-TB from as long as 18 months or longer to 6 months and the number of pills comprising treatment by nearly 95 percent, all while significantly improving cure rates and toxicity profiles compared to the previous standards of care.This year, WHO updated guidelines for the treatment of drug-resistant TB to include pretomanid-containing regimens. Additionally, a study published in the New England Journal of Medicine showed that BPaL maintained efficacy with reduced dosage of linezolid, one of the drugs in the regimen. This is just one of the key tools that are essential to strengthen efforts against TB, especially as the recent 2022 Global TB Report reported that the number of TB and drug-resistant TB cases have risen for the first time in many years.For other fascinating global health news delivered to your inbox weekly and to stay abreast of developments in 2023 and beyond, sign-up now to receive GHTC’s R&D News Roundup newsletter.Image credits: PATH/Rocky Prajapati, PATH/Eric Becker, PATH/Christopher Nelson, PATH/Georgina Goodwin, PATH/Rocky Prajapati, PATH/Matthew Dakin

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, Medicines for Malaria Venture and the Africa Centres for Disease Control and Prevention (CDC) signed a memorandum of understanding for providing technical support to African manufacturers for the development of antimalarial drugs. The support is aimed at helping improve the quality of antimalarial products to meet World Health Organization’s (WHO’s) standards in order to increase the use of locally produced drugs and make them eligible for bulk procurement by global institutions, as well as to address the high burden of malaria on the continent. This effort is also part of a wider initiative to increase African manufacturing after COVID-19 uncovered the risks of the continent’s over-reliance on imported drugs. The Bill & Melinda Gates Foundation and the Coalition for Epidemic Preparedness Innovations (CEPI) are investing US$30 million in Aspen Pharmacare Holdings Limited to support the manufacturing of routine and outbreak vaccines for Africa. Through a ten-year agreement with the Serum Institute of India, Aspen will use the investment to manufacture and distribute the routine Pneumococcal, Rotavirus, Polyvalent Meningococcal, and Hexavalent vaccines, as well as support technology-transfer activities and build regional vaccine manufacturing capacity for potential future outbreaks. The investment underlies a wider effort to ensure vaccine manufacturing capacity and supply of affordable vaccines on the continent. Joining a growing call for action in response to the increasing threat of antibiotic resistance, WHO recently published the Global antimicrobial resistance and use surveillance system (‎GLASS)‎ report: 2022, which identified a high level of antibiotic resistance in bacteria that can cause fatal bloodstream infections and an increasing level of resistance in bacteria that can cause common infections. The report echoes a wider concern about the need for the development of new antibiotics for newborn babies to address the up to 570,000 deaths and estimated three million cases of neonatal sepsis each year, many of which occur in the absence of effective antibiotics due to rising antimicrobial resistance.