Sanofi, J&J abandon trial of E coli vaccine after poor data

Johnson & Johnson and Sanofi's vaccine for preventing invasive disease caused by the problem pathogen Escherichia coli looks all but defunct after the two partners halted a phase 3 trial.

In a statement issued this morning, the partners confirmed that an analysis of interim data from the E.mbrace study by its independent data monitoring committee (IDMC) found that the vaccine candidate didn't demonstrate sufficient efficacy and would be discontinued, other than to carry out safety follow-up.

It's a major blow to a keenly anticipated programme that aimed to tackle the huge public health problem of extraintestinal pathogenic E coli (ExPEC), which is estimated to cause around 10 million cases of invasive disease every year and is responsible for around 40% of bacterial sepsis cases. Figures suggest that someone in the world dies of sepsis every three seconds.

The search for a vaccine has become particularly important as antimicrobial resistance (AMR) is on the rise in ExPEC, with standard cephalosporin-based treatment losing its efficacy, raising the risk that patients progress to sepsis, septic shock, and organ failure.

Sanofi's head of vaccine R&D, Jean-François Toussaint, acknowledged this, noting that E coli sepsis is "a devastating disease" with no preventive measure currently available.

"We are disappointed to see that the vaccine was not associated with sufficient efficacy to support the trial continuation, and we will work tirelessly to understand the factors behind the IDMC's finding and to share further analysis once available," he added.

E.mbrace started in 2021 and was intended to enrol around 18,500 patients aged 60 years and over who were at risk of invasive E coli disease (IED) due to recurrent urinary tract infections, but who were otherwise in stable health. The cohort was due to be followed for three years.

In 2023, Sanofi paid $175 million upfront for shared rights to the ExPEC9V bioconjugate vaccine, designed to protect against nine separate strains of E coli, and has since parted with around $75 million in development milestones along with R&D funding. The company said it will take a $250 million charge in its fourth quarter 2024 results as a result of the trial termination.

A US study published in 2023 stated that more than three-quarters of patients presenting in hospital with IED were aged over 60, with the urinary tract being the source of infection in around half of them.

This age group was most likely to show signs of organ failure, and resistance to at least one standard antibiotic was seen in 66% of cases, with almost 41% also resistant to a drug from a second antimicrobial class as well, making a shift in emphasis from treatment to prevention a necessity.