Global Leaders Group lays out steps to boost antibiotic development, access

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Antibiotic research & development
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The Global Leaders Group (GLG) on Antimicrobial Resistance (AMR) last week issued a series of recommendations to address shortfalls in the antibiotic pipeline and boost access to new antibiotics and diagnostics.

The GLG, which was formed in 2020 to strengthen global political leadership on AMR and includes heads of state and leaders from the public and private sectors, says the recommendations can serve as the basis for advocacy and action in advance of the upcoming United Nations High-Level Meeting on AMR in September. The group adds that the recommendations should be seen as part of a comprehensive strategy against AMR that includes prevention and stewardship.

"The lack of access to existing and innovative antibiotics is a contributor to the inappropriate use of antibiotics and the development of antimicrobial resistance," the group wrote. "The GLG believes that antibiotics should be considered as global public goods, which should galvanize collective action to address the antibiotic pipeline and access crisis."

R&D targets, push and pull incentives, regulatory frameworks

The six recommendations, based on interviews with GLG members and additional experts and stakeholders, are aimed at incentivizing innovation, stimulating research and development (R&D), and safeguarding access to antibiotics. The first recommendation calls for the World Health Organization (WHO) to work with governments and industry to establish shared R&D targets for antibiotics and diagnostics, with implementation roadmaps and target product profiles.

Recommendation 2 calls for public and private funders to increase funding for push incentives to support antibiotic and diagnostic R&D efforts, while recommendation 3 urges G7 and G20 countries to establish pull incentives—such as the subscription-style antibiotic payment model being implemented in the United Kingdom—that would support R&D and enable access to antibiotics and diagnostics.

The other recommendations from the GLG call for national and regional regulatory bodies to adopt regulatory frameworks to facilitate development and approval of antibiotics; urge the WHO, national governments, donors, and partners to significantly expand efforts to increase access to essential antibiotics while ensuring their appropriate use; and call for stronger global coordination across the R&D and access continuum.

The GLG believes that antibiotics should be considered as global public goods, which should galvanize collective action to address the antibiotic pipeline and access crisis.

Peru declares dengue health emergency

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Peru's health ministry yesterday declared a dengue emergency for 20 of the country's 25 regions, a step that allows the government to free up more resources to support its response.

Peru fumigation
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In a statement, health officials said the health emergency declaration will be in effect for 90 days, and they will allocate at least $42 million toward response actions, including mosquito control and outbreak investigation.

So far, more than 31,000 suspected dengue cases have been reported, 17,965 of them confirmed and 32 fatal.

Cesar Vasquez, the country's health minister, said, "The unusual heat wave and the absence of winter have generated a perfect panorama for the spread of dengue."

Earlier this month, the Pan American Health Organization (PAHO) said dengue activity in the region is already outpacing record levels in 2023. In an update, it noted that cases are rising in 11 Americas countries, including Peru.

Takeda and Biological E partner to ramp up vaccine production

In other dengue developments, Takeda yesterday announced a partnership with India-based Biological E to speed the production of the Qdenga vaccine.

Takeda said in a statement that Biological E would make up to 50 million Qdenga doses a year, with a goal of producing 100 million doses a year in multidose vials by 2030. Officials said the multidose vial formulation offers logistical advantages for national vaccine programs.

Gary Dubin, MD, president of Takeda's global vaccine business unit, said, the company's goal it to make the vaccine broadly available. "Within the last year, we've successfully launched in private markets, are now launching in some public programs, and working with partners to support a broader public health impact."

Brazil, a country hit hard by the disease, recently spelled out a plan to offer dengue vaccine though its public system, the first country to do so.

PAHO rates Western equine encephalitis risk in the Americas as moderate

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The Pan American Health Organization (PAHO) recently published a risk assessment of Western equine encephalitis (WEE), following the recent detection of human cases in Argentina and Uruguay, their first in many years.

culex tarsalis
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The infections followed an increasing number of outbreaks in animals in Argentina and Uruguay. An isolated animal infection was also reported in Brazil in an area that borders both countries.

WEE infections in humans typically range from asymptomatic to moderate, but in rare instances, the severe form of the disease can result in aseptic meningitis or encephalitis. There are no specific treatments or vaccines for WEE.

Seven deaths in Argentina

So far, 73 human WEE infections have been reported, 69 in Argentina and 4 in Uruguay. All have been reported in areas where the mosquito-borne virus is affecting animals. Seven deaths have been reported in Argentina. Most of the illnesses were reported in people who are older and have underlying health conditions.

Birds are the natural hosts of the virus, which can pass to people and animals through infected mosquitoes. PAHO said that, in South America, rodents and bats could also serve as reservoirs.

El Nino pattern among outbreak contributors

PAHO said several factors may be contributing to increased WEE activity, including a seasonal shift in Culex tarsalis mosquitoes feeding from birds to mammals. So far there are no data to suggest an increase in mosquito density. PAHO added that other factors could include increased rainfall and temperatures due to climate change, deforestation, and increased urbanization.

The group said the overall health risk to human health in the region is moderate. It also noted that the risk of further spread is high, partly due to environmental factors related to the El Nino weather phenomenon and climate change, which could pave the way for geographic expansion of the mosquitoes that spread the disease.

CARB-X announces funding for gonorrhea vaccine

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CARB-X, the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, announced it's giving $2.2 million to LimmaTech Biologics AG, a Swiss biotech firm, to fund the development of its novel vaccine candidate targeted to prevent Neisseria gonorrhoeae infections.

Gonorrhea is one of the most common sexually transmitted infections (STIs), with more than 82 million people diagnosed annually. Patients do not always have symptoms, and untreated infections can result in pelvic inflammatory disease, chronic pain, infertility, and an increased risk of contracting other STIs.

"Gonorrhea is becoming increasingly resistant to treatment, which reinforces the pressing need for a highly effective and safe vaccine that can protect against this serious and pervasive pathogen," said Franz-Werner Haas, PhD, CEO of LimmaTech, in a press release from CARB-X. "We believe our proprietary vaccine technology offers advantages in efficacy, production scalability and simplicity to include multiple antigens that can effectively address bacterial infectious disease threats."

Gonorrhea is becoming increasingly resistant to treatment, which reinforces the pressing need for a highly effective and safe vaccine.

Ceftriaxone is the only currently available antibiotic that can treat drug-resistant strains of the bacteria.

"Vaccines are powerful tools in the prevention of bacterial infections. LimmaTech’s vaccine project, if successful, could prevent the disease, and significantly curb the spread of resistant bacteria across the globe," said Erin Duffy, PhD, the research and development chief of CARB-X.

LimmaTech is also developing vaccines against other infections increasingly resistant to antibiotics, including Staphylococcus aureus and Shigella.

FDA rejects new drug application for cefepime-taniborbactam

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Manufacturing issues have led the US Food and Drug Administration (FDA) to reject a New Drug Application (NDA) for cefepime-taniborbactam, a combination antibiotic under review as a potential treatment for urinary tract infections (UTIs) caused by multidrug-resistant bacteria.

In a press release late last week, Venatorx Pharmaceutical and Melinta Therapeutics said the FDA issued a Complete Response Letter to the NDA requesting additional chemistry, manufacturing, and controls (CMC) and related data about the drug, testing methods, and manufacturing process. The companies said the FDA did not identify clinical safety or efficacy issues, nor did it request any new clinical trials.

Developed by Venatorx, of Malvern, Pennsylvania, cefepime-taniborbactam combines a fourth-generation cephalosporin antibiotic with a beta-lactamase inhibitor. The results of a phase 3 trial recently published in the New England Journal of Medicine found the combination antibiotic was superior to meropenem in patients with complicated UTIs. Venatorx submitted the NDA to the FDA in August 2023 based on the results of that trial.

The drug is also viewed as a potential treatment for other infections caused by drug-resistant gram-negative bacteria and other organisms. In October 2022, Venatorx received a $318 million contract from the Biomedical Advanced Research and Development Authority to develop cefepime-taniborbactam for treating melioidosis, a respiratory disease caused by the bacterium Burkholderia pseudomallei.

Company says it will work with FDA

"While we are disappointed with this setback, we maintain utmost confidence in cefepime-taniborbactam," said Venatorx CEO Christopher J. Burns, PhD. "We are already hard at work generating the additional requested CMC data, and we will continue to work closely with the FDA so that we can make this important new medicine available to patients as quickly as possible."

Venatorx and Melinta, of Parsippany, New Jersey, announced a partnership in November 2023 to commercialize cefepime-taniborbactam in the United States.

"We are committed to our plans of supporting the US commercialization of this drug, which we believe when approved, will offer healthcare providers an important therapy for adult patients suffering from complicated urinary tract infections, including acute pyelonephritis caused by susceptible gram-negative microorganisms," Melinta CEO and President Christine Ann Miller, MBA, said.

Data: Adults with kidney injury fared better with COVID than with other illnesses

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Patient on dialysis
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Adults hospitalized for COVID-19 and associated acute kidney injury (AKI) had lower rates of major adverse kidney events (MAKE), long-term decline in kidney function, and death than patients with AKI related to flu or other diseases, concludes a study at five hospitals in a single healthcare system published yesterday in JAMA Internal Medicine.

Yale University researchers analyzed the electronic health records of 9,624 AKI patients to compare the risk of MAKE, worse kidney function, and death in the next 2 years among those with COVID-19 with those with other illnesses. Patients were hospitalized from March 2020 to June 2022, and their results were compared with those hospitalized for influenza A or B and AKI from October 2016 to January 2020.

MAKE was defined as worse kidney function (estimated glomerular filtration rate [eGFR] decline of at least 25% after hospital release or kidney failure requiring dialysis). Average patient age was 69.0 years, 51.5% were women, 10% had COVID-19 and AKI, 3% had flu and AKI, and 87% had AKI and other diseases.

Replication in broader cohorts as well as assessment of the effects of other kidney dysfunction markers (eg, proteinuria) and the association of COVID-19−specific therapeutics with kidney function trajectory are worth investigating in future studies.

Relative to patients in the other two groups, patients with COVID-19 and AKI were slightly younger and had a higher baseline eGFR, more underlying illnesses, more severe illness, and longer hospital stays.

69% lower risk of death in COVID patients

In unadjusted analyses, death rates were 5.4% for COVID-AKI group, 9.0% for flu-AKI patients, and 9.8% for those with AKI related to other diseases. At 2-year follow-up, death rates were 7.4%, 16.7%, and 13.9%, and respectively. COVID-related AKI patients had a 33% lower risk of MAKE, a 22% lower risk of poorer kidney function, and 69% lower risk of death than those with AKI due to other diseases.

"Replication in broader cohorts as well as assessment of the effects of other kidney dysfunction markers (eg, proteinuria) and the association of COVID-19−specific therapeutics with kidney function trajectory are worth investigating in future studies," the researchers wrote.

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