Breakthroughs Blog: Tuberculosis

Last week, the Global Antibiotic Research & Development Partnership (GARDP) and Debiopharm announced a new partnership to advance the development of Debio1453, a novel, first-in-class antibiotic targeting Neisseria gonorrhoeae, as rising cases and the continued spread of multidrug-resistant strains have turned gonorrhea into a growing health challenge globally. Almost all the antibiotics used to treat gonorrhea caused by N. gonorrhoeae have been rendered ineffective due to antimicrobial resistance, with the bacteria now beginning to develop resistance to the last remaining effective treatment. If successful, this drug candidate could help revive the critically lacking pipeline of new antibiotics, one of many new drugs that will be needed to ensure that innovation can outpace the rapid emergence of antibiotic resistance.  Sedia Biosciences announced last week that the World Health Organization (WHO) has granted prequalification status for its rapid, oral HIV test, enabling global procurers to buy the test and ensure widespread access to the technology. The single-use test, which detects antibodies to HIV-1 and HIV-2 in as little as 20 minutes, is intended for health care providers to be able to use at the point of care in resource-limited settings. Beyond its rapid readout time, the test is less invasive, complicated, and painful than blood testing because it uses oral fluid (saliva), making it simpler and more tolerable for patients. With support from the Coalition for Epidemic Preparedness Innovations (CEPI), the Serum Institute of India and the University of Oxford are partnering to create the largest-ever reserve of an investigational vaccine for Rift Valley fever, against the backdrop of a deadly ongoing outbreak and the threat of future outbreaks of the disease, for which there are no licensed human vaccines. The Serum Institute will manufacture up to 100,000 doses of the University of Oxford’s ChAdOx1 RVF candidate, which is among the most advanced investigational vaccine candidates in the pipeline. Ten thousand doses are set to be used in a planned clinical trial of the candidate in outbreak-affected areas, while the remaining doses will serve as a reserve available for clinical testing during future outbreaks. 

GSK has shared the results of two highly anticipated Phase 3 studies investigating its potential “functional cure” for chronic hepatitis B, which affects more than 250 million people worldwide and is a leading cause of liver cancer. The drug bepirovirsen was found to be safe and more effective than the current standard of care in the studies, which included more than 1,800 patients across 29 countries. Bepirovirsen was also found to be capable of achieving a “functional cure,” defined in the studies as no hepatitis B surface antigens (a marker of active infection) detectable in the blood and no detectable genetic material from the virus for at least 24 weeks after treatment ends. The drug, if successfully approved, has the potential to transform treatment for people with chronic hepatitis B. Last week, IAVI announced that the first doses of experimental HIV vaccine antigens were administered in a Phase 1 trial designed to advance a new strategy for HIV vaccine development. Researchers from IAVI and Scripps Research are investigating the hypothesis that highly specialized vaccine immunogens, delivered in a specific sequence, can target critical cells in the immune system and train them to produce broadly neutralizing antibodies against HIV, which scientists widely agree could provide broad protection against the virus. The trial will take place at six clinical sites in South Africa, carried out by a group of African clinical research centers. A team of researchers led by the University of Virginia has shared findings that could transform the treatment of sepsis, the leading global cause of death, in Africa. With a research grant from the US National Institutes of Health, the scientists followed patients with HIV-related sepsis in eastern Africa for five years. They found that the most common cause of sepsis was tuberculosis and that immediate treatment, even before tuberculosis diagnosis, significantly improved survival rates. The findings show that this strategy of immediate tuberculosis treatment could save lives, as well as underline the need for more accurate rapid diagnostic tests for tuberculosis. 

At the recent Union World Conference on Lung Health, TB Alliance presented the results of a Phase 2 clinical trial showing that the novel antibiotic candidate sorfequiline has the potential to improve tuberculosis (TB) treatment when combined with pretomanid and linezolid in people with drug-sensitive TB. The regimen was more effective than the current standard of care, and sorfequiline also demonstrated greater activity than bedaquiline, a key component of the BPaL regimen, a previous breakthrough that drastically reduced treatment time for most drug-resistant TB. This new treatment could shorten TB therapy even further. TB Alliance is working with partners ahead of the launch of a Phase 3 trial next year. Researchers at the University of California San Diego and partners have developed a new method to combat antibiotic-resistant bacteria, which could pave the way for developing alternatives to traditional antibiotics for treating a wide range of deadly infections, as the global threat of antimicrobial resistance continues to grow. The researchers used bacteriophages (or phages), which are viruses that infect and kill bacteria. Phages have been used to treat bacterial infections for more than 100 years but are usually limited in the bacterial strains they can successfully target. Researchers overcame this by allowing the pages to evolve alongside bacteria in a controlled laboratory setting for 30 days, enabling the phages to adapt their bacterial defenses, becoming more effective at killing a wide variety of bacterial strains, including drug-resistant ones, and better at suppressing bacterial growth for extended periods. Researchers at Indiana University have developed a molecular test that can simultaneously detect three dangerous fungi much faster than traditional methods, helping patients receive accurate, timely treatment against this growing global challenge. The test works by targeting genetic regions unique to each fungus, and it was much faster and more accurate than standard methods, a key advance as fungal infections are often mistaken for other respiratory illnesses. While the test still needs to be clinically validated in further studies, the research team believe it could eventually fill a major gap in fungal diagnostics. 

The World Health Organization's (WHO's) TB Vaccine Accelerator Council recently published a new report calling for action to ensure equitable access to future tuberculosis (TB) vaccines currently in the pipeline. While the only licensed vaccine for TB is 100 years old and has limited effectiveness in adolescents and adults, as of September, there are 16 candidate vaccines in clinical development, six of which are in Phase 3 trials. WHO estimates that a vaccine for adolescents and adults that is at least 50 percent effective could avert up to 76 million TB cases and 8.5 million deaths over 25 years. However, as the report claims, global demand could far exceed supply in the initial years after a vaccine is approved because there is no designated funding for such a rollout in low- and middle-income countries most affected by TB, which are already facing significant funding shortfalls. In anticipation of these potential bottlenecks and barriers to access, the report identifies six solutions to encourage countries with a high burden of TB, manufacturers, and other funders and stakeholders to start preparing now for the rollout to ensure future vaccines can reach people who need them faster. In a Phase 1 randomized controlled trial, an experimental intranasal vaccine against multiple H5N1 avian flu strains generated a broad immune response, demonstrating the potential of such a vaccine to play a major role in preparing for outbreaks of emerging viruses with evolving strains, as H5N1 continues its worrying spread. The University of Maryland research team tested the vaccine against a placebo in 40 adults between 18 and 45, finding that the vaccine was safe, well-tolerated, and stimulated immunity at various doses. One group received a vaccine dose combined with an adjuvant, an ingredient used to trigger a stronger immune response, and their immune systems were better able to neutralize infected cells for longer, suggesting that the use of an adjuvant could be a promising approach that might allow for lower doses, which could stretch limited vaccine supplies in the event of an outbreak. Last week, IAVI published new findings from the first-in-human Phase 1 clinical trial of its Lassa virus vaccine candidate, which show that one dose of the vaccine triggers robust and long-lasting immunity and is safe. There are no vaccines or treatments currently licensed against the dangerous illness, which causes thousands of deaths in endemic West Africa and has been designated as a priority pathogen with pandemic potential. The trial enrolled 114 volunteers in Liberia and the United States. The candidate, now undergoing a Phase 2a trial in West Africa, is currently the most advanced Lassa fever vaccine candidate in the pipeline and uses the same platform as Merck’s single-dose Ebolavirus vaccine, which is approved in more than a dozen countries.