Breakthroughs Blog: Antimicrobial resistance

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 first vaccine against chlamydia—one of the most common sexually transmitted infections—has proven to be safe and effective in a phase 1 clinical trial. The trial tested two different versions of the vaccine and though both elicited an immune response, one performed better than the other. Further testing will proceed with that version. Due to the complexity of the bacterium, researchers posit that a successful vaccine must provoke a strong immune response both with antibodies to fight bacteria outside of the cells, and immune system protein and cells to help clear the bacteria from infected cells. Approximately 131 million people are infected with chlamydia each year. If left untreated, it can cause chronic pelvic pain and infertility in women. Last Wednesday, the US Food and Drug Administration (FDA) approved a new drug, pretomanid, for treatment of highly drug-resistant tuberculosis (TB). Pretomanid, developed by TB Alliance, was approved as part of a three-drug, six-month, all-oral regimen, which also includes bedaquiline and linezolid—collectively known as BPaL. In a clinical trial, 95 out of 107 patients had a successful outcome after six months of treatment with the regimen. The historical treatment success rate is 34 percent. Pretomanid is only the third FDA-approved anti-TB drug in more than 40 years, though TB remains the world’s number one infectious disease killer. In what is being hailed as a landmark announcement, two antibody-based therapies have proven to dramatically improve the survival rate of people newly infected with Ebola in a clinical trial conducted in the Democratic Republic of the Congo (DRC)—raising hope that the yearlong epidemic in the DRC and future outbreaks of the virus can be more easily contained. The two treatments, REGN-EB3, developed by Regeneron Pharmaceuticals, and mAb114, developed by the National Institute of Allergy and Infectious Diseases, were among four therapies tested as part of a clinical trial that began in November. These two treatments will now be offered to all patients, with experts recommending that the other two therapies involved in the clinical trial be stopped. The yearlong Ebola outbreak in the DRC, which was declared a public health emergency by the World Health Organization last month, has infected 2,800 people and killed more than 1,800 people.

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 National Institutes of Health (NIH) is hoping that an ambitious effort to create a “Google” for biomedical research could help researchers connect the dots between health data sets to unlock new scientific insights and discoveries. Launched by NIH in 2016, the Biomedical Data Translator program is attempting to create a tool that would integrate different data sources, ranging from electronic health records to clinical trial results, and apply machine learning techniques to reason through the information allowing researchers to make connections between not previously associated datasets and identify trends across them. So far, the program has awarded approximately US$17.5 million to 19 institutions across the country working to integrate and organize years of data. The initial feasibility phase of the project is set to end this year. Surveys conducted by the World Health Organization (WHO) in 18 countries from 2014 to 2018 reveal an alarming surge in resistance to critical HIV drugs. In the past four years, 12 countries in Africa, Asia, and the Americas have surpassed the acceptable levels of drug resistance against two key HIV drugs, efavirenz and nevirapine—showing more than ten percent of adults with HIV have developed resistance to these drugs in these nations. Though the causes of drug resistance are unclear, the co-author of a WHO report on the survey’s findings suggests drug-resistant HIV may develop when people interrupt treatment. In response to this evidence, WHO recommends that countries use dolutegravir as first-line treatment against HIV since the likelihood the virus will develop resistance is lower with dolutegravir than with other antiretrovirals. The Coalition for Epidemic Preparedness Innovations (CEPI) will provide biotech company, Valneva, with up to $23.4 million to fund the development of a single-dose, live-attenuated vaccine for Chikungunya—a mosquito-borne disease which causes fever, severe joint pain, muscle pain, and fatigue. The funding from CEPI will support vaccine manufacturing and late stage clinical development to help accelerate regulatory approval of the vaccine for use in regions where outbreaks occur. Valneva plans to maintain a stockpile of the vaccine and transfer its manufacturing to Chikungunya-endemic regions. Since Chikungunya re-emerged in 2004, approximately 3.4 million cases in 43 countries have been identified.

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. To help tackle antimicrobial resistance (AMR), the Global Antibiotic Research & Development Partnership (GARDP) announced its new “5 BY 25” strategy to mobilize global stakeholders to raise the €500 million needed to develop five new antibiotic treatments by 2025. According to a GARDP press release, drug-resistant infections cause at least 700,000 deaths per year globally and addressing the growing threat of AMR will be key to achieving universal health coverage and the Sustainable Development Goals. With this new strategy, GARDP aims to develop and make accessible five new treatments that will focus on the priority pathogens identified by the World Health Organization, along with current unmet needs for diseases and key populations. In a promising step towards an HIV and AIDS cure, researchers from Temple University and the University of Nebraska have successfully eliminated HIV from the DNA of infected mice using genome editing technology combined with a slow-release virus suppression drug. Researchers administered a treatment called LASER ART, or long-acting, slow-effective release antiretroviral therapy to suppress HIV cells from replicating in mice engineered to produce human T cells susceptible to the virus. The research team deployed the drug across several weeks to target tissue in the spleen, bone marrow, and brain where latent HIV reservoirs are likely to occur. The researchers then used CRISPR-Cas9, a gene-editing tool, to eliminate the remaining infective cells from the subject’s DNA. By the end of the study, researchers had successfully eliminated HIV from nine out of 23 mice. Researchers are now working on a version of the study with primates. If their methods continue to be successful, clinical trials could follow as soon as next summer. Heads of state from the world’s largest economies committed to advance global health priorities at this year’s G20 Summit in Osaka, Japan. In the G20 Osaka Leaders’ Declaration, they included commitments to move towards universal health coverage by bolstering primary health care and access to medicines, promote healthy aging by preventing noncommunicable diseases, improve emergency preparedness and response, provide support for the countries affected by the current Ebola outbreak, and identify better models for antimicrobial drug research and development. Participants in the summit, described as the “premier forum for international economic cooperation,” includes leaders from 19 countries and the European Union, as well as guest countries and international organizations.

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 World Health Organization’s (WHO) new Science Division unveiled a Health Product Profile Directory—an online resource to guide the research and development of new technologies to combat neglected diseases and other health threats, including antimicrobial resistance and diseases that pose a pandemic threat. The Health Product Profile Directory is a free, searchable database of target product profiles for needed health products to tackle the world’s most pressing global health issues. Each product profile outlines eight to ten key characteristics for development of various health products, including vaccines, medicines, and diagnostics. The directory currently contains 196 product profiles developed by 24 agencies, 91 of which are focused on infectious diseases. In this editorial piece, Dr. Madhukar Pai also discusses whether the product profiles should address affordability, the opportunity to leverage the directory to tap into the potential of emerging innovators in the Global South, and ways to improve the new WHO resource. Every year, 5.4 million people are bitten by snakes. Between 81,000 and 138,000 die as a result, and of those who survive, 400,000 suffer lifechanging injuries. Two years ago, WHO formally classified snakebite as a neglected tropical disease and later this month it will launch a global strategy aimed at halving the number of deaths and cases of disability caused by snakebite by 2030. Last week, two major funding announcements for snakebite research were made public. Wellcome Trust announced a new £80 million program to transform the way snakebite is managed globally, and the UK Department for International Development (DFID) released £9 million to fund the development of a universal snake antivenom. The DFID-funded consortium—which includes the International AIDS Vaccine Initiative, the Liverpool School of Tropical Medicine, and snakebite specialists from Kenya, Nigeria, the United States, and India—will leverage the technology and processes that led to the discovery of drugs to combat HIV to develop new antivenom therapies. It will run through 2021, when a pre-clinical prototype of antivenom is expected. TB Alliance was awarded a Center of Excellence in Translational Research grant by the National Institute of Allergy and Infectious Diseases to support the development of two new clinical stage tuberculosis (TB) drug candidates. The grant, spaced out over five years, will provide US$5.5 million in the first year and reach a total of $28.4 million by 2024. With this grant, TB Alliance and its research partners will focus on the development of compounds that address drug-sensitive and multidrug-resistant strains of TB. “Expanding the global portfolio of new TB drug candidates, from which we can assemble tomorrow’s shorter and simpler cures, is crucial in the fight against TB,” said Dr. Mel Spigelman, president and CEO of TB Alliance.