FDA mulls extending Arexvy approval to people ages 50 to 59

News brief

The US Food and Drug Administration (FDA) has accepted GSK's application for priority review for extended use of its respiratory syncytial virus (RSV) vaccine Arexvy in adults ages 50 to 59 at higher risk for complications.

older man vaccine
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In a press release today, GSK said its application is supported by promising results from a phase 3 trial in the age-group. Arexvy is currently approved for use in adults ages 60 and older. GSK added that if approved, Arexvy would be the first RSV vaccine recommended for use in people in their fifties. The FDA expects to make a decision by June 7, 2024.

Drug regulators in the European Union and Japan are also reviewing GSK's applications for use in people ages 50 to 59 at higher risk for RSV.

Lab tests link company's cheese products to lengthy Listeria outbreak

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Federal health officials today announced that they and state partners are investigating a multiyear, multistate Listeria monocytogenes outbreak tied to a California's company's cotija and queso fresco cheeses.

recalled cheese
Photo: Courtesy of Rizo-Lopez Foods

In a statement, the Centers for Disease Control and Prevention (CDC) said that 26 illnesses have been reported from 11 states, with onset dates as far back as June 2015 and extending through December 2023. Of patients with available information, 23 were hospitalized, and 2 deaths were reported—one from California and the other from Texas.

The CDC said it investigated the outbreak in 2017 and 2021, which pointed to the types of cheeses, but there weren't enough details to identify a specific brand. Officials reopened the investigation in January following a report of an illness in December, and routine sampling by the Hawaii Department of Health turned up a match in cheese samples from Rizo-Lopez Foods and identified the outbreak strain.

Interviews with 22 sick patients found that 16 remembered eating queso fresco, cotijo, or similar cheeses, and of those who remembered specific brands, three said they had consumed Don Francisco brand cheese, which is one of the brands made by at Modesto, California-based Rizo-Lopez Foods. Also, Food and Drug Administration (FDA) inspections of Rizo-Lopez Foods identified the outbreak strain on a container where cheeses were kept.

On January 11, the company recalled its aged cotija cheese following Hawaii's identification of a positive sample. Today, the company recalled all cheese and other dairy products made at its facility. Products—sold under 13 brand names—were distributed nationally and were available at deli counters. It urged consumers to check their refrigerators and freezers for the products and to dispose of them.

Promising clinical results for novel antiviral onradivir for flu

News brief

Chinese researchers yesterday reported promising results in a phase 2 trial of a novel antiviral called onradivir for treating seasonal flu. The team reported its findings yesterday in The Lancet Infectious Diseases.

The drug, developed by Zhongsheng Pharmaceutical, inhibits the flu virus's polymerase basic protein -2 (PB2) subunit, which prevents replication. The researchers note that onradivir is currently the only antiviral candidate making its way through clinical trials that targets PB2 and that more flu antiviral options are needed, given the ongoing threat of antiviral resistance with other flu drugs.

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For the study, they enrolled 205 healthy adults ages 18 to 65 from multiple clinical sites who had a confirmed flu infection between December 7, 2019, and May 18, 2020. Researchers noted that the COVID-19 pandemic and related restrictions reduced the study's enrollment. Participants were randomized to one of four groups: 200 milligram (mg) twice a day, 400 mg twice a day, 600 mg once a day, and placebo. They took the medication within 48 hours of symptom onset.

All treatment groups had decreased median time to symptom alleviation, but only the 600-mg group showed statistical significance compared with the placebo group. Diarrhea was the most common side effect and was seen in 40% of participants.

The team concluded that onradivir shortened symptoms and reduced viral load in patients with uncomplicated flu, especially at the 600-mg dose. A phase 3 trial of the drug is under way with a larger study group to compare the 600-mg onradivir dose with oseltamivir and a placebo.

Practical challenges remain

In a related commentary, two experts with the University of Maryland School of Medicine Center for Vaccine Development and Global Health—Lynda Coughlan, PhD, and Kathleen Neuzil, MD, MPH—wrote that the results for onradivir are promising. But they noted practical challenges regarding clinical use, including early flu identification, for optimal treatment benefit.

They also said the results need to be replicated in groups at higher risk for flu complications, including older people and those with underlying health conditions.

Probe confirms imported eye drops as source of extensively drug-resistant Pseudomonas outbreak

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Person using eye drops
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A team led by the Centers for Disease Control and Prevention (CDC) yesterday published the details of its investigation into the source of a multistate outbreak of carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa linked to artificial tears. The findings appeared in Clinical Infectious Diseases.

The investigation by researchers with the CDC, the Food and Drug Administration (FDA), and several state and local health departments identified a total of 81 case-patients from 18 states in the outbreak, which stretched from May to November 2022 and was originally linked to an ophthalmology clinic in Los Angeles. Nearly a third of the patients (26) were treated at one of three healthcare facilities in three states. Four of 54 case-patients with clinical cultures died within 30 days of culture collection, 4 of 18 patients with eye infections had to have their eyes removed, and an additional 14 suffered vision loss.

Overall, the use of artificial tears was reported by 61 of 70 case-patients with information, and 43 of 56 with brand information reported using Brand A—a preservative-free, over-the-counter (OTC) product manufactured in India. A 1:1 case-control study conducted with 16 case-patients identified in the largest healthcare facility cluster found that cases had five times greater odds of exposure to artificial tears than controls (crude matched odds ratio [OR], 5.0; 95% confidence interval [CI], 1.1 to 22.8).

Trace-back investigation confirms source

Whole-genome sequencing of isolates from case-patients and opened and unopened Brand A bottles showed the isolates were genetically related, and an FDA inspection of the Brand A manufacturing site identified "multiple deficient practices" as the likely sources of contamination.

"The combination of epidemiology and laboratory evidence, including the close genetic relatedness of isolates from case-patients across multiple states and from unopened Brand A product, indicates Brand A artificial tears was the outbreak source," the authors wrote.

They add that proposed legislative changes by the FDA that would strengthen regulatory requirements for sterile manufacturing facility inspection prior to the distribution of OTC products could help prevent similar outbreaks in the future.

Study finds racial, ethnic minorities underrepresented in antibiotic trials for Staph infections

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A systematic review of randomized controlled trials (RCTs) on antibiotics for Staphylococcus aureus infections found widespread underrepresentation of racial and ethnic minorities, researchers reported late last week in Clinical Infectious Diseases.

Meredith Newlove / CDC

The study, led by researchers with Duke University School of Medicine and Yale School of Public Health, reviewed 87 RCTs of antibacterial drugs used to treat S aureus infections published from 2000 to 2021 to determine the race, sex, and ethnicity of participants. The researchers then calculated participation to incidence ratios (PIRs) by dividing the percentage of study participants in each group by the percentage of the disease population in each group. Under-representation was defined as a PIR of less than 0.8.

Of the 87 RCTs included, 82 (94.2%) reported participant sex, (69) 79.3% reported race, and 20 (23%) reported ethnicity data. Only 17 studies (19.5%) enrolled American Indian/Alaskan Native participants. While most RCTs had adequate or overrepresentation of female and White participants, median PIRs indicated that Asian (0.36) and Black (0.37) participants were under-represented compared with the incidence of methicillin-resistant S aureus (MRSA) infections in those subgroups.

Analysis of factors associated with underrepresentation of Black participants identified larger study size, international sites, industry sponsorship, and phase 2/3 trials compared with phase 4 trials as factors. Black participants were nearly five times less likely to be included in phase 2/3 trials compared with phase 4 trials (odds ratio, 4.57; 95% confidence interval, 1.14 to 18.3).

Increased enrollment of marginalized groups needed

The study authors say the level of underrepresentation of Black and other racial and ethnic subgroups they found "calls into question the generalizability of data used to evaluate the efficacy and effectiveness of antibacterial drugs for S. aureus infections," noting that Black populations experience higher rates of invasive MRSA infections compared with Whites. They say more effective strategies are needed to increase enrollment of marginalized groups.

"Our study reinforces the importance of enhancing strategies to optimize enrollment and reporting on diverse participants in RCTs of antibacterials used for S. aureus infections," they concluded.

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