Breakthroughs Blog: Malaria

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, the Global Antibiotic Research and Development Partnership (GARDP) and Bugworks announced an agreement to accelerate the development of a broad-spectrum antibiotic compound, BWC0977, which has shown potential in treating patients with serious infections caused by pathogens that have become increasingly hard to treat due to growing antibiotic resistance to multiple classes of drugs. GARDP has agreed to invest up to $20 million for further clinical and pharmaceutical development. If the antibiotic is ultimately approved, Bugworks plans to launch it in the United States, the European Union, Japan, and China, while GARDP will manufacture and commercialize the compound in 148 countries, including nearly all low- and middle-income countries, with both partners emphasizing their hope to ensure rapid access and appropriate use in high-burden countries like India and South Africa, where access to novel antibiotics is often limited. Promising results from a phase 2a trial of a broad-spectrum influenza vaccine candidate were published in The Lancet Infectious Diseases last week. The trial, which tested the biopharmaceutical company Osivax’s candidate vaccine OVX836 at various doses in 137 healthy adult subjects, found that it was safe and immunogenic at all dose levels tested, warranting further testing in larger phase 2b and 3 trials. The vaccine, which fits the universal influenza target product profile set by the US National Institutes of Health, could be a promising new tool to address influenza if further tests continue to confirm its potential.New research found that a novel mRNA-based malaria vaccine, which takes a unique approach by using an ingredient developed to boost the immune response to cancer, was effective in mouse models. The novel vaccine generated an immune response in mouse models, prevented infection with one form of the Plasmodium parasite, and unlike many other malaria vaccines, proved effective in animals that had already been exposed to malaria, underscoring the potential of this tool in malaria-endemic regions. While this research is still in very early stages, scientists plan to next test the vaccine in humanized mouse models and hope to be able to advance to clinical trials in the coming years.

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 month, Brazil became the first country in the world to introduce tafenoquine, the first new single-dose treatment for P. vivax malaria developed in 70 years. Tafenoquine, developed by GSK and Medicines for Malaria Venture (MMV) in partnership with local researchers in Brazil, improves upon the previous treatments, which had major issues with adherence due to higher complexity and longer duration. The local Brazilian research partners also developed a new point-of-care test to identify a hereditary condition that can cause hemolytic anemia in those who take tafenoquine or one of the previous treatments, primaquine. After the approval and registration of tafenoquine in Brazil in 2019, field studies conducted over the last few years found extremely high levels of compliance with the new treatment protocol of routine testing to inform treatment, and similar feasibility studies are starting around the world, which will hopefully provide further evidence to improve global and national malaria guidelines and programs.The world’s first trial for a potential treatment for Crimean-Congo hemorrhagic fever has launched in Turkey. There are currently no specific approved drugs or vaccines and limited funding for R&D for the virus, which was named a priority pathogen by the World Health Organization. It is endemic in many countries in Africa, the Middle East, and Asia and has a mortality rate as high as 40 percent. The phase 1 trial will test the safety and potential dosages of two different drugs in multiple combinations, hopefully leading to more advanced trials or at least initiating momentum for more research to address the virus.This week, the US Food and Drug Administration approved a monoclonal antibody, Beyfortus, to protect infants and young children from respiratory syncytial virus (RSV). The single-injection antibody therapy, developed by AstraZeneca and marketed in the United States by Sanofi, showed strong results in phase 3 clinical trials. If the treatment gets a further recommendation from the Centers for Disease Control and Prevention, the drug could greatly reduce hospitalizations and deaths caused by RSV, which is the leading cause of hospitalization of babies in the United States. Beyfortus, has already been licensed in the European Union, the United Kingdom, and Canada, and other technologies for RSV, including a vaccine for pregnant people are also aiming to reduce the global burden of the virus.

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. Gavi, the World Health Organization (WHO), and UNICEF have announced that an initial 18 million doses of the world’s first malaria vaccine, RTS,S/AS01, will be rolled out in 12 African countries, where the risk of child illness and deaths from malaria is highest. The vaccine, which will be produced by GlaxoSmithKline and Bharat Biotech, is expected to arrive in the initial countries in late 2023. A further 16 countries have also asked for access and are expected to receive it once production has scaled up. Another malaria vaccine, R21, developed by Oxford University is currently awaiting WHO prequalification. In the coming years, both vaccines are expected to play a key role in the fight against malaria alongside other tools.A study published last week found that injections of broadly neutralizing antibodies in children living with HIV can improve the protective effects of antiretroviral drugs, marking the first time broadly neutralizing antibodies have been tested in combination with antiretroviral drugs in a pediatric population. The treatment suppressed cells that contained the virus and were capable of reactivating, paving the path to further research that could confirm the use of this method as a supplemental or alternative treatment for HIV in children. The publication of these findings follows recent research, which has focused on testing broadly neutralizing antibodies as a treatment for adults with HIV. Worldwide, about 1.7 million infants and children are living with HIV.Last week, Gavi confirmed that some of the $2.6 billion remaining in COVAX, the COVID-19 vaccine delivery initiative, could be redirected towards furthering investigational vaccine candidates for Marburg and Ebola Sudan, as well as a hexavalent vaccine that would offer protection against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, and the inactivated polio vaccine. The investments for Marburg and Ebola Sudan will hopefully contribute to ensuring clinical trials in future outbreaks, especially after the scrapped trials during the recent Marburg and Ebola Sudan outbreaks.

Pregnant women in their first trimester are at risk of malaria Eileen Buxton is a Ghanaian nurse who contracted malaria while pregnant with twins. As a health care professional, she recognized the symptoms such as high fever, severe nausea, and vomiting. She sought care and was given artemether-lumefantrine, a medicine that was recently recommended by the World Health Organization (WHO) to treat malaria in the first trimester of pregnancy.Unfortunately, the situation where medicines are available and determined to be safe for use in first-trimester pregnancy is uncommon. According to the Concept Foundation, since the 1990s, only two drugs have been developed specifically for pregnant women. Furthermore, in the clinical research stage of medicine development, pregnant women, especially those in their first trimester, have been historically excluded for fear of causing harm to the mother and the baby. As a result, health care professionals and pregnant women are left with limited information, making it difficult to make informed decisions about the best course of treatment. Well-tolerated and effective antimalarials, as well as medicines for other diseases, must be developed and made available, accessible, and affordable for pregnant women like Eileen. Malaria infection and treatment during the first trimester of pregnancyMalaria, although preventable and treatable, can become fatal if left untreated, and in pregnancy, the disease has severe consequences for both the mother and the baby she is carrying. Malaria in pregnancy (MiP) can result in the severe, rather than uncomplicated, form of the disease for the mother, resulting in gestational hypertension, premature labor, miscarriage, and the fetus being small for its gestational age. Newborns can be born prematurely and with low birth weight, leading to further health complications, such as cognitive delays. During the first trimester, women are especially at risk of malaria infection because they are unprotected, as no preventive therapies are available until later in pregnancy. Data show that around 65 percent of cases of MiP appear late in the first trimester because the placenta becomes more susceptible to infection, demonstrating a clear need for recommended medicines that can both prevent and treat women in early pregnancy. Although the aforementioned effects of malaria in the second and third trimesters are well known, there has been little data collected on the effects of malaria in the first trimester: few women in malaria-endemic countries attend health facilities in early pregnancy due to a mix of cultural and logistical factors, creating an obstacle to generating research.Preventive therapies for the first trimester are urgently needed: currently, there are none. Intermittent preventive treatment of malaria in pregnancy, an intervention used in sub-Saharan Africa, is only recommended by WHO from the second trimester onward to protect pregnant women from the disease.And although WHO recently recommended the artemisinin-based combination therapy (ACT) artemether-lumefantrine for use in the first trimester, the organization’s Strategy to respond to antimalarial drug resistance in Africa also points out that most countries rely on this drug and thus recommends using a wider range of ACTs to mitigate the development of drug resistance. Ethics and regulatory frameworks for including pregnant women in clinical researchThe four main ethical principles of clinical research are beneficence, nonmaleficence, autonomy, and justice. These principles must be adhered to when designing clinical trials that safely and equitably include pregnant women in their first trimester. In fact, excluding this population perpetuates a cycle of underrepresentation in clinical research, while including them adheres to the principle of justice by ensuring that individuals, regardless of status or condition, have equal access to the benefits of medical research. Drug development takes, on average, 10 to 15 years before registration. When pregnant women are excluded from clinical research, there are no data on how well tolerated or effective it is for pregnant women when the drug reaches market. The COVID-19 pandemic demonstrated that it is possible to rapidly develop and distribute drugs, and with the Sustainable Development Goals (SDGs) set to expire in seven years, the malaria community needs to work at an accelerated pace to achieve Target 3.3 of the SDGs: end the epidemics of AIDS, tuberculosis, malaria, and neglected tropical diseases and combat hepatitis, water-borne diseases, and other communicable diseases. Greater priority must be placed on expediting the discovery, development, and delivery of medicines that meet the needs of at-risk groups, like pregnant women in their first trimester.Global health has experienced a paradigm shift: it is now widely acknowledged that pregnant women must be protected through, and not from, research, a principle that is underscored by recent international commitments. In 2022, at the 75th World Health Assembly, WHO member states adopted Resolution 75.8: Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination. While it does not specifically mention pregnancy, this resolution provides a basis for countries in both the Global North and the Global South to develop clinical ecosystems that are “health-needs driven, evidence based, well designed and well implemented and be guided by established ethical guidance.”In 2021, the G7 Health Ministers adopted the G7 Therapeutics and Vaccines Clinical Trials Charter, which commits to “stronger collaboration in large-scale international trials to enable greater diversity of participants, including pregnant people and children” and supporting low- and middle-income countries, where malaria is most prevalent, in sustainably strengthening capacity. Malaria in pregnancy remains a major public health concern that demands urgent attention and action from global health stakeholders. Clinical research plays a critical role in advancing the development of effective interventions with an adequate safety profile. Ensuring that pregnant women are part of this research from the start can help save millions of lives and adhere to fundamental principles of justice and equity.