Breakthroughs Blog: Medicines

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R&D News Roundup email.Dexamethasone, an inexpensive, decades-old drug is showing promise for treating COVID-19, per unpublished, preliminary results from a study called Recovery that was funded by the United Kingdom. The preliminary results indicated that the drug reduced the risk of death for patients on ventilators by 35 percent, those receiving oxygen by 20 percent, and overall mortality by 17 percent. Immediately following the results, the United Kingdom granted approval for use of the drug to treat COVID-19. According to FiercePharma, UK officials have enough dexamethasone stockpiled to treat 200,000 patients.  A recent study lends support to anecdotal evidence that blood type and genetics may be linked to worse outcomes from COVID-19 illness. Last Wednesday, a team of European researchers published a study in The New England Journal of Medicine indicating that people with type A blood have a 45 percent higher risk of catching COVID-19 and sliding into respiratory failure and people with type O blood have a 35 percent lower risk of developing respiratory failure compared to people with other blood types. Scientists are still unsure why blood type might be correlated with COVID-19 outcomes, but a nascent hypothesis is that it could be linked to blood clotting risk. The researchers also found that a cluster of genes are associated with higher risk of developing severe COVID-19 by 77 percent.A project led by researchers from Scripps Research, GHTC member IAVI, and the University of California San Diego School of Medicine published research in Science detailing a set of antibodies discovered in recovered COVID-19 patients that provide powerful protection against SARS-CoV-2. In theory, the antibodies could be given to patients who are just developing the illness to prevent progression to severe disease and to protect people who are at higher risk for contracting COVID-19. To discover the antibodies, the scientists isolated more than 1,000 distinct antibody-producing immune cells, obtained genetic sequences from these cells to produce more antibodies, and then tested the antibodies’ effectiveness against blocking the virus in vitro. The researchers discovered several antibodies that, even in small quantities, could block the SARS-CoV-2 virus. The work was funded by the US National Institutes of Health, IAVI, and the Bill & Melinda Gates Foundation, among others.

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. As part of Operation Warp Speed, the Trump Administration has selected five top COVID-19 vaccine candidates to receive priority government support. The candidates include mRNA-1273 (Moderna and the National Institute of Allergy and Infectious Diseases), AZD-1222 (AstraZeneca and Oxford University), Ad26 SARS-Cov-2 (Johnson & Johnson), and candidates from Merck/IAVI and Pfizer. The Merck/IAVI and Pfizer candidates have not yet received federal funding, but as selected companies, they will receive access to government support to advance their programs. The mRNA-1273 and AZD-1222 candidates are already in phase 2 clinical trials and are expected to reach phase 3 in July. Officials anticipate that each vaccine will be tested on 30,000 individuals in phase 3 trials, some of which may take place outside the United States. An official announcement about the selection of these five companies is expected from Operation Warp Speed in the next few weeks.Convalescent plasma, sourced from patients who have recovered from COVID-19, did not demonstrate significant effectiveness as a treatment in the first randomized clinical trial evaluating its use. The Wuhan-based trial, however, fell short of its target recruitment because of containment of the outbreak and only enrolled 103 of the 200 patients needed to demonstrate a clinically meaningful result. In the same journal, Dr. Arturo Casadevall of the Johns Hopkins School of Public Health said that, though there was no significant improvement, the study gave “potentially hopeful signals” and that convalescent plasma should be tested in combination with antiviral drugs.The World Health Organization (WHO) launched at the end of May the COVID-19 Technology Access Pool, or C-TAP, a global project to share intellectual property and speed the research, development, and deployment of new vaccines, tests, treatments, and other health tools for COVID-19. The voluntary pool was initiated by Costa Rica and is supported mostly by low and middle-income countries and only a few high-income countries. Notably, many countries that are leading the research race for new tools, including the United States, the United Kingdom, France, Germany, and Switzerland, have not supported C-TAP. Meanwhile, some leaders from the pharmaceutical industry have dismissed the project while other groups, such as the Médecins Sans Frontières’ Access Campaign, have given praise.

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. In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. An HIV vaccine candidate has shown promising results in human trials. A study in the Lancet found that this “mosaic” vaccine—comprised of pieces of different HIV strains—produced an anti-HIV immune system response in tests on 393 people. Further testing is required to determine if the immune response produced can prevent the HIV infection in people. In the next phase of testing, 2,600 women from southern Africa who are at risk of contracting HIV will receive the vaccine. This is one of only five HIV vaccine candidates to ever make it to this stage of efficacy trials. Paraguay has eliminated malaria, becoming the first country in the Americas to achieve this milestone in approximately a half-century, according to the World Health Organization. Public health officials have credited the national health system’s ability to quickly detect cases and determine whether they had been transmitted locally or imported as critical to Paraguay’s success. Though Paraguay has thwarted the threat of malaria for the moment, nine countries in the Americas reported at least a 20 percent increase in malaria cases between 2015 and 2016. Complacency and lack of political will in other countries in the region threaten the fight against malaria. Scientists at the California Institute for Biomedical Research are testing a new approach to tackling malaria and other insect-borne diseases using a group of veterinary drugs called isoxazolines. When administered orally to animals, isoxazolines remain in the bloodstream for up to three months, killing blood-sucking insects by damaging their nervous systems. The researchers believe isoxazolines have the potential to dramatically reduce the transmission of malaria, as any mosquito who bites a person who has taken this drug would be killed before transmitting the disease to other people. The study published by the California Institute for Biomedical Research estimates that giving 30 percent of the population isoxazolines in countries affected by malaria could prevent more than 70 percent of malaria infections. Researchers believe that isoxazolines are safe for human consumption and plan to continue to evaluate their efficacy.

A Kenyan women poses with her baby son Ethan, who was in the hospital for 2 weeks with malaria. Photo: PATH/Gabe BienczyckiGlobal efforts to tackle malaria have proved hugely successful over the last 16 years, with more than 6.8 million lives saved. Yet, these gains are at risk. As we are seeing across all microbial diseases, the development of drug resistance is a huge threat. There is an urgent need to discover new medicines with novel mechanisms of action able to treat resistant parasites to ensure malaria patients can continue to be cured and we can continue the drive to end malaria for good. The traditional approach to drug discovery is clothed in secrecy, as scientists compete to find the next billion-dollar blockbuster. For "diseases of poverty" such as malaria, however, the low commercial value of the end product means that the need for confidentiality and competition is reduced, if not counterproductive. Scientists across the world are now starting to open up drug discovery research for these diseases with exciting results. MMV’s approach for malaria Medicines for Malaria Venture (MMV) is a nonprofit organization working with partners around the world to bring forward the next generation of antimalarials to tackle challenges like drug resistance. Our approach to drug discovery is “open innovation.” Over the years, we have built up a community that shares data and assays among a set (or subsets) of partners for a given project or projects. These open innovation projects are not transparent to the outside world, rather they operate within contractual “bubbles,” with a semi-permeable membrane securing confidentiality. For example, from 2008 to 2014, MMV and partners conducted an extensive screening campaign to stir up new chemistry for drug discovery projects. More than six million compounds were screened against the parasite, generating tens of thousands of new chemical starting points. One series, known as the aminopyridines, were identified through a screen performed by scientists from Griffith University, Australia. The series was then selected and explored further by a team of scientists at the University of Cape Town, South Africa, working in collaboration with scientists at MMV. With parasitological support from the Swiss Tropical and Public Health Institute and drug metabolism expertise from Monash University, Australia, the South African team selected the most promising compounds from the series for optimization and re-testing. In 2014, it became the first new antimalarial medicine to enter phase 1 studies in Africa. Today, preparations are being made to begin a phase IIa trial on this promising compound as a single dose cure. The advantage of this open innovation approach is that it allows MMV to tap into a wide range of expertise and existing research facilities—as well as share early proprietary knowledge among a select group of partners—together with risk, cost, and effort.Opening up beyond malariaWith the success of the screening campaign and open innovation approach for malaria research, we were keen to apply the learnings and lessons to other neglected diseases. In 2010, following the screening campaign, GlaxoSmithKline, the Genomics Institute of the Novartis Research Foundation, and St Jude Children's Research Hospital in Memphis, Tennessee, released the details of 20,200 compounds active against malaria into the public domain. The research community responded largely with enthusiasm, yet many felt blocked without physical access to the compounds. MMV responded in December 2011 by launching the open access Malaria Box, making 400 diverse compounds divulged by the screening campaign available for free. Since its launch, more than 250 copies of the Malaria Box have been delivered to researchers in 30 countries to catalyze malaria and neglected diseases drug research. All that was asked in return was that the researchers continue the virtuous cycle of sharing and collaboration by releasing their data into the public domain. Researchers screening the Malaria Box found hits against 16 different protozoa, seven helminths, nine bacterial and mycobacterial species, as well as the dengue mosquito vector and human cancer, many of which are undergoing further research today. The big lesson here is that compounds active against one disease (malaria) can be repurposed for a range of other diseases. Based on this and the successful uptake of the Malaria Box, MMV launched the Pathogen Box in 2015, comprising 400 compounds with activity against malaria or one of a range of other neglected diseases. This box, alongside several Challenge Grants awarded to promising projects, are not only catalyzing neglected diseases drug discovery, but also helping to support researchers in disease-endemic countries and bringing forth future generations of scientists.In this vein, our next initiative is the Pandemic Box, which will include antiviral and antibiotic compounds—again, at no cost to researchers. The goal is to provide chemical starting points for drug discovery for diseases like Zika and Ebola, as well as repurpose compounds for malaria and neglected diseases. This will be a joint project between MMV and Drugs for Neglected Diseases initiative. Can we open up further?Exploring the possibility of working completely in the open, in another project with Dr. Mat Todd of the University of Sydney, Australia, we have broken the membrane and created an Open Source Malaria drug discovery project. Essentially, everything related to the project is entirely in the public domain so that anyone, anywhere can follow and contribute. The idea is that it will work by “natural selection”—anyone can work on the shared data and, over time, the project will evolve. In this case, the best ideas will be prioritized and a new candidate drug for malaria will hopefully emerge.So far, the project has taught us that there is a enormous willingness to contribute and share expertise, but money and resources are still rate limiting. If people don’t synthesize compounds in a reasonable timeframe, research comes to a halt. MMV believes in open source approaches, but realizes they need a sustainable supply of resources and more importantly, focus. With limited resources, it is important to prioritize the most promising ideas.Working in partnership to end malaria for goodThese different knowledge-sharing projects clearly demonstrate that through collaboration we can achieve so much more than if we go at it alone. Since 2010, MMV’s collaborations have delivered 17 candidate molecules for malaria. This has created a strong pipeline, but many more candidates are needed if we are to succeed in defeating malaria. We continue to enlarge our partnership network and explore new ways to open up drug discovery research for the global good.