Research Roundup: HIV Crispr therapy, MPP COVID-19 pill agreement, BARDA influenza funding

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 World Health Organization (WHO) has announced a clinical trial of one or possibly two experimental vaccines designed to protect against the rare Sudan strain of the Ebola virus that has been identified in the recent, rapid outbreak in Uganda. The trial could begin within weeks depending on the Ugandan government’s permission, which is expected soon, as well as regulatory and ethics review approvals. The trial was announced by the WHO’s Health Emergencies Program, which has been conferring to identify vaccines that are far enough along in their development to undergo clinical testing. There are six vaccine candidates in development that are designed to target the Sudan strain, only half of which have advanced to the stage of human clinical trials. Of those, a candidate developed by the Sabin Vaccine Institute and the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases is the furthest along in its development. Dengue resurged across Asia following a period of lower transmission due to reduced mobility because of COVID-19 restrictions, but an exciting vaccine has the potential to make huge strides in reducing the burden of the disease not only in the region but around the world. In August, Indonesia became the first country in the world to approve Takeda’s Qdenga, or TAK-003, vaccine for use against dengue in 6- to 45-year-olds. Qdenga showed incredibly promising results in clinical trials and is under review by the European Medicines Agency and other regulatory agencies in dengue-endemic countries, although it is yet to receive WHO prequalification. The vaccine addresses the complexity of dengue’s four strains by using a weakened version of the DENV 2 strain as its base and including genes from the other three strains.In 2020, a clinical trial in South Africa testing PrEP as a shot delivered every few months found incredible success with results showing high efficacy compared to the daily pill. The drug used in the trial (long-acting cabotegravir or Cab-LA) made by ViiV Healthcare has only been awarded regulatory approval in the United States to date. Access to the shot in low- and middle-income countries has been hampered by the company’s decision to not grant licenses for generic makers to produce the drug at a lower cost. The company has made an agreement with the Medicines Patent Pool that permits three or fewer companies to make generic versions of the drug in 90 low- and middle-income countries, but it could take at least three years for regulatory approval. Viiv Healthcare has submitted its drug for WHO prequalification, which could speed up this approval process.