Breakthroughs Blog: Medicines

At GHTC, we get to read stories every day about incredible innovations in global health. Most of the technologies we see are inventive, some are revolutionary, and a few are so unusual, one might think they were ripped from the pages of a science fiction novel. Now, we’re testing how well you know these global health technologies with our annual Halloween game: the TRICK or TREATment quiz.For each question, we will present a description of a global health technology. Choose TREATment if you believe this innovation exists. Choose TRICK if you think we are trying to pull one over on you and, instead, the product is still in development or is just a figment of our imagination. 

Malaria in pregnancy threatens the health of mothers and babiesWhen a woman finds out she is pregnant, it is often an exciting, emotional, and nerve-racking time. For women in malaria-endemic countries, however, there is an additional concern: the risk of contracting malaria during pregnancy. This was a major worry for Kenyan mother Elyne Kaingu. Fortunately, during her second pregnancy, she received intermittent preventive treatment of malaria in pregnancy (IPTp) at the health clinic, enabling her to have a malaria-free pregnancy. However, not all women are as fortunate as Kaingu.According to the World Health Organization’s (WHO’s) 2021 World Malaria Report, 34 percent of the more than 33 million pregnancies worldwide in 2020 were exposed to malaria, meaning more than 11 million women and babies were at risk for the serious complications that malaria in pregnancy (MiP) may entail, including anemia, the development of severe malaria, and risk of miscarriage or low infant birth weight. Insufficient prevention and treatment options for MiP Despite the urgent need, options for preventing and treating MiP are currently limited. Pregnant women are usually excluded from clinical trials to protect them and their babies from potential adverse effects of new drugs in development, making it difficult to determine the safety and appropriate dose to guide recommendations of new and existing drugs for use in pregnant women. While WHO recommends artemisinin-based combination therapies (ACTs) to treat uncomplicated malaria and sulfadoxine-pyrimethamine (SP) for IPTp for women in their second and third trimesters, these treatments fall short in some critical areas: neither is recommended for use in the first trimester of pregnancy1 and SP should not be used by pregnant women with HIV/AIDS receiving prophylaxis against opportunistic infections or by women in areas where SP drug resistance is reported.Protecting and treating pregnant women: Researching, repurposing and recombining antimalarials  To improve the availability of well-tolerated and effective antimalarials for pregnant women, changes in drug development approaches are urgently needed. Through MMV’s MiMBa strategy, the product development partnership is advocating for and advancing several innovative research approaches.What has first been required is a mindset shift—a clear agreement to change the way we approach de-risking of compounds so that there is robust data on pregnancy as soon as possible in the drug development process. Starting at the earliest phase (discovery), MMV is prioritizing new antimalarials for progression to development based on their low-risk profile for birth defects. In addition, MMV is using translational pregnancy models to optimize and accelerate their clinical development by providing information on the potential need to adjust drug dosing for pregnant women, as well as the possibility of fetal exposure. Further, MMV performs developmental and reproductive toxicity studies that evaluate the effects of potential drugs on one complete life cycle (from conception in one generation through the following generation) earlier in the development process. Compounds which are shown to be well-tolerated in developmental and reproductive toxicity studies will be evaluated in pregnant women. It is hoped that if compounds can be appropriately de-risked, then in future dedicated clinical trials in pregnancy might be conducted in parallel to phase 3 trials, also known as confirmatory studies, which “aim to confirm the efficacy and safety of the candidate compound in a large patient population.” This approach would allow for the collection of information to establish the benefit/risk balance of a new antimalarial at an earlier stage and will help ensure that the needs of pregnant women are addressed in a more timely and equitable manner in the future.Existing antimalarials: Filling the data gapMMV has undertaken research on existing drugs for their potential use in pregnant women. With its pharmaceutical partner Shin Poong and other research partners, MMV conducted a real-life study (CANTAM) on pyronaridine-artesunate (Pyramax®) in five countries in Africa with results indicating high safety, tolerability, and efficacy for the 11 women who were unknowingly pregnant. Finally, MMV is currently providing input in an ongoing study, PYRAPREG, led by the University of Sciences, Techniques and Technologies of Bamako, which is looking at the efficacy and safety of four ACTs, including Pyramax, in the second and third trimesters of pregnancy. Further, MMV is supporting follow-up studies on ACTs already on the market. For example, MMV and the Liverpool School of Tropical Medicine’s Timika facility in Indonesia continues to monitor women during and after their pregnancies.Finally, MMV has set up a pregnancy registry, launched last year in Kenya with the Liverpool School of Tropical Medicine and extended to Burkina Faso at the beginning of 2022. Through this registry, MMV aims to obtain robust data on the use of a range of ACTs for the treatment of uncomplicated malaria in pregnancy. The information generated will serve to better understand the benefit/risk ratio and contribute to informing policymakers, regulators, clinicians, and pregnant women on the use of ACTs, particularly during the first trimester. According to Hellen Barsosio, a senior clinical research scientist based in Kenya, “Pregnancy registries are vital in providing safety information on drugs and vaccines used during pregnancy, particularly within the first trimester, a critical period for the growing baby due to the limited safety data available by the time drugs reach the market.”Facilitating access to antimalarialsFor antimalarials to be useful in preventing and treating MiP, healthcare workers and patients must be aware of their protective effects and be able to access them. MMV works with governments, pharmaceutical companies, and implementing partners to ensure that antimalarials are available as quickly as possible after launch, especially in hard-to-reach areas. A recent success in facilitating access to antimalarials for pregnant women is the achievement of WHO prequalification for SP by Universal Corporation Ltd, a Kenyan pharmaceutical company, supported by Unitaid and MMV. Universal Corporation Ltd is the first pharmaceutical company in Africa to achieve prequalification for SP. As alternatives to SP advance, it will be crucial to enable manufacturers in endemic countries to produce quality-assured medicines so that they are readily available for pregnant women. The World Health Summit serves as a reminder that those who are the most vulnerable to diseases must be at the center of drug discovery and development efforts. Developing antimalarials to address the needs of pregnant women is vital to achieving malaria eradication by ensuring that everyone can access the care they need. 1. On 25 November, WHO released its updated guidelines for malaria, which include a strong recommendation for the use of an ACT, artemether-lumefantrine, to treat uncomplicated malaria in women in their first trimester

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. The Medicines Patent Pool (MPP) and ViiV Healthcare last week announced a new voluntary licensing agreement that would allow for generic manufacturing and distribution of long-acting cabotegravir in an effort to expand access to the HIV prevention drug. Long-acting cabotegravir—an injectable form of preexposure prophylaxis, or PrEP—can provide two months of protection against HIV infection with a single shot, while most other forms of PrEP require daily pills. The new licensing agreement between the United Nations-backed MPP and ViiV will let select generic manufacturers apply for sublicensing to develop, manufacture, and supply generic forms of the drug in 90 countries—pending regulatory approvals—where the HIV burden and potential use of cabotegravir is the highest.The Coalition for Epidemic Preparedness Innovations (CEPI) is supporting an initiative to develop a standardized approach to test the performance of vaccines being used or in development against monkeypox. The new funding, announced days after the World Health Organization declared monkeypox a public health emergency of international concern, will go to the UK Medicines and Healthcare products Regulatory Agency and the UK Health Security Agency to pursue tools able to assess the strength and duration of immune responses generated by current vaccines, as well as for tests used to detect monkeypox antibody levels. These tools will subsequently be made available to the global scientific community for free, apart from administration fees, enabling a standardized assessment between countries documenting vaccine performance against monkeypox, according to CEPI.Researchers have identified a specific area of the SARS-CoV-2 spike protein as a good target for pan-coronavirus vaccines, making a promising advance in the development of a shot to protect against COVID-19 variants and common colds. A universal coronavirus vaccine would need to induce antibodies that recognize and neutralize a wide range of viruses—a challenge, given the complexities of the coronavirus family, according to scientists. In the new study, scientists investigated whether antibodies targeting the S2 subunit of SARS-CoV-2’s spike protein could also neutralize other coronaviruses, including a strain of the common cold as well as several COVID-19 variants, and found promising results among mice. The researchers plan to continue to study the method as potential pan-coronavirus vaccine target and evaluate how it could be integrated with currently licensed vaccines.

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. Following the remarkable success of the first COVID-19 vaccines, developed at unprecedented speeds, investment in next-generation shots has so far fallen short, according to some experts. Nasal vaccines, in particular, experts say could prove more effective at preventing COVID-19 infections than intramuscular shots, as they concentrate immune protection in the upper airway and induce mucosal immune responses where the virus typically enters the body. Several nasal vaccine candidates are in development in the United States—though primarily remain in preclinical or early-stage clinical trials—as well as globally, including phase 3 trials in India and China. The National Institute of Allergy and Infectious Diseases, for example, is funding early research on a protein-based nasal spray as well as an mRNA vaccine delivered into the nose using nanoparticles, though any successful nasal vaccine is likely years away from becoming available.As monkeypox cases continue to rise globally, experts and leaders are looking at health technologies with potential to combat the virus—including repurposed smallpox vaccines that have begun to be deployed, predominantly in high-income countries. In addition to vaccines, scientists are evaluating existing drugs that could serve as treatments against monkeypox, for which there are no specific treatments licensed. A recent study in JAMA analyzed several preexisting drugs, including antivirals brincidofovir and tecovirimat, both of which have been tested among monkeypox patients in the past with varying success. The ongoing uncertainty surrounding treatments for the new outbreak highlights the lack of evidence-based therapeutics for monkeypox, according to the journal article, as well as the inequities in the global response as countermeasures have been stockpiled by high-income countries but remain limited in monkeypox-endemic countries.In a new study, researchers describe how a Lassa virus protein drives infection by harnessing a cellular protein in human hosts, as well as identify how future therapies could target this interaction to treat patients. The research suggests that disrupting the link between Lassa polymerase—a protein encoded by the virus—and a specific host protein it interacts with—GSPT1—could stop Lassa virus infection. In pursuit of this, the research team identified an existing drug candidate, CC-90009, that has been shown to destroy GSPT1 proteins and is currently being examined in clinical trials as a cancer therapy. In early experiments, CC-90009 significantly reduced Lassa virus growth without obvious cell toxicity, and researchers plan to continue evaluation in animal models. There is currently no antiviral drug that specifically targets Lassa virus.