Gepotidacin meets efficacy goal in phase 3 trial for uncomplicated gonorrhea

News brief

British drugmaker GSK announced earlier this week that its investigational oral antibiotic for uncomplicated gonorrhea met its primary efficacy end point in a phase 3 trial.

Preliminary results from the EAGLE-1 trial showed that gepotidacin, a first-in-class triazaacenaphthylene antibiotic that works by inhibiting bacterial DNA replication, demonstrated non-inferiority to the current standard-of-care gonorrhea treatment (intramuscular ceftriaxone plus oral azithromycin) in patients with uncomplicated urogenital gonorrhea. The results are based on a primary end point of microbiologic response at the test-of-cure visit 3 to 7 days after treatment.

The company said the safety and tolerability of gepotidacin was consistent with results from earlier trials.

Rising resistance to current treatments

Global estimates indicate there are more than 82 million new gonorrhea cases each year, and resistance to the currently recommended treatment is rising. That's a problem because the Neisseria gonorrhoeae bacterium has developed resistance to every other antibiotic that's been used for treatment, and no other options are currently available.

"With rising incidence rates and concern around growing resistance to existing treatments, gonorrhoea poses a threat to public health globally," Chris Corsico, GSK's senior vice president for development, said in a company press release. "These positive headline results demonstrate the potential for gepotidacin to provide a novel oral treatment option in the face of rising resistance and for patients who cannot take other treatments due to allergies or intolerance."

GSK is also developing gepotidacin as a treatment for uncomplicated urinary tract infections (uUTIs). In two other recent phase 3 trials—EAGLE-2 and EAGLE-3—the antibiotic showed non-inferiority and superiority to nitrofurantoin in women with uUTIs.

Company officials say they will present the data from the EAGLE-1 trial at an upcoming scientific meeting.

These positive headline results demonstrate the potential for gepotidacin to provide a novel oral treatment option in the face of rising resistance and for patients who cannot take other treatments due to allergies or intolerance.

Chikungunya vaccine recommended for US travelers in outbreak settings

News brief

The Center for Disease Control and Prevention (CDC) vaccine advisory group today recommended the chikungunya vaccine for people ages 18 and older who will be traveling to a country or territory experiencing an outbreak of the disease.

chikungunya virus
NIAID/Flickr cc

The vote passed with 12 yes votes and 1 abstention.

Last November the Food and Drug Administration (FDA) approved the nation's first chikungunya vaccine, which is a live attenuated vaccine made by Valneva that is given as one intramuscular dose.

Chikungunya is an emerging health threat that has sickened more than 5 million people over the past 15 years, mainly in areas where the mosquito that carries the virus is endemic. The disease isn't usually fatal but can cause fever, plus debilitating joint pain that can last for months.

As part of ACIP's recommendation, the group also said that use of the vaccine may be considered for certain people traveling to a country or territory where chikungunya has been known to circulate in the past 5 years. They include people older than 65, especially those with underlying health conditions who are likely to have at least moderate exposure to mosquitoes, and people who will be staying in affected areas for 6 months or more.

Group also recommends vaccine for certain lab workers

In a separate vote, which passed unanimously, the group recommended chikungunya vaccination for lab workers who are potentially exposed to the virus.

Infections in lab workers have been rare in the United States. Among the few cases, two involved needlesticks in scientists who were working with mice and one involved a forceps prick in a lab worker who was dissecting mosquitoes, a CDC expert said today.

Antiplatelet therapy linked to less severe COVID outcomes

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blood clot
Anne Weston, Francis Crick Institute / Wellcome Images

Polish researchers publishing today in Scientific Reports suggest that patients receiving antiplatelet therapy before contracting COVID-19 were less frequently hospitalized in the intensive care unit (ICU), developed shock less often, and had lower 3-month mortality. The study was conducted in 2020 and 2021, before the widespread use of vaccine in Poland.

The study compared outcomes among hospitalized COVID patients who were taking antiplatelet therapy prior to infection (274 patients) and matched controls who had never received antiplatelet therapy.

Thrombosis, or blood clotting, has been indicated as a factor in COVID-19 mortality, and the authors hypothesized that antiplatelet therapy may protect against severe outcomes linked to thrombosis, as platelets play a major role in hemostasis, thrombosis, and inflammatory response, they said.

In the study, 94% of patients were taking a form of acetylsalicylic acid, including aspirin, at the time of COVID infection.

3-month mortality better in antiplatelet group

In-hospital mortality for both groups of patients was similar, with deaths occurring among 53 (19%) and 64 (23%) of the antiplatelet therapy and no-antiplatelet groups, respectively.

Patients who had been on antiplatelet therapy, however, were less likely to go to the ICU (9% vs 15%), and develop shock (9% vs 15%). There was also a lower 3-month mortality (31% vs 39%) for the antiplatelet therapy group (hazard ratio 0.69, 95% confidence interval, 0.51 to 0.93.)

More cardiovascular events were reported in the short- and long-term in the antiplatelet therapy group, but the authors suggest this is likely due to preexisting comorbidities.

The overall prognosis was better in the AP [antiplatelet] group.

"Despite the greater number of comorbidities and vascular events during hospitalization, the overall prognosis was better in the AP [antiplatelet] group," the authors wrote.

 

 

 

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Study: Staph bloodstream infections are deadlier in women

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Staphylococcus aureus
NIAID / Flickr cc

A systematic review and meta-analysis found that women with Staphylococcus aureus bacteremia (SAB) had an increased risk of death compared with men, researchers reported yesterday in JAMA Network Open.

S aureus is the leading cause of death from bloodstream infections, and mortality in SAB patients has been linked with several risk factors, including increasing age, infective endocarditis, hemodialysis dependence, and persistent bacteremia. To determine whether female sex is associated with increased mortality risk in patients with SAB, researchers with Duke University and Leiden University Medical Center in the Netherlands reviewed 89 studies involving 132,582 SAB patients. The main outcome was mortality at or before 90 days following SAB.

An 18% increased risk in mortality

Unadjusted mortality data from 81 studies revealed a 12% increased mortality risk in women compared with men (pooled odds risk [OR], 1.12; 95% confidence interval [CI], 1.06 to 1.18). The 32 studies with adjusted mortality data that accounted for additional patient characteristics and treatment variables showed an 18% increased mortality risk compared with men (pooled adjusted OR, 1.18; 95% CI, 1.11 to 1.27). No evidence of publication bias was observed.

The study authors say that while they didn't address the underlying causes of sex difference in mortality risk in the study, the difference could be due to a variety of social or biological factors that should be further explored in future studies.

"Fundamental research on biological sex differences in immune response or pharmacology, examinations of sex-based differences in management of SAB, and better reporting of sex-specific outcomes in randomized clinical trials are necessary to better understand the observed sex-specific differences in mortality among patients with SAB," they wrote.

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