Biopharmaceutical company Crestone Pharmaceuticals last week announced positive topline results from a phase 2 trial of its investigational drug treatment for Clostridioides difficile infection (CDI).

The trial evaluated the safety and efficacy of two different dosages of CRS3123, a small-molecule protein synthesis inhibitor, administered twice daily in adults diagnosed with a primary episode or first recurrence of CDI. Vancomycin was the comparator drug.

Among the 43 patients in the primary intention-to-treat analysis, 28 of 29 (97%) who received one of the two dosages of CRS3123 achieved clinical cure at the day 12 test-of-cure visit, compared with 13 of 14 (93%) who were treated with vancomycin. In addition, only 4% of CRS3123 patients experienced CDI recurrence at day 40, compared with 23% in the vancomycin group. CRS3121 was also well-tolerated, with no serious treatment-emergent adverse events reported. 

Minimal microbiome disruption

One of the advantages of CRS3123 over current therapies is its narrow spectrum, which enables it to target C difficile bacteria and inhibit toxin production with minimal disruption to other microbes in the gut. Vancomycin is a broad-spectrum antibiotic known to disrupt the gut microbiome.

CDI is the most common healthcare-associated infection in the United States, with an estimated 500,000 cases occurring each year. Roughly 1 in 6 CDI patients experience a recurrence within 2 to 8 weeks.

"Treatment of C. difficile infection remains in urgent need of agents that spare normal gut microbes, so they can reconstitute the microbiome and prevent further recurrences of CDI," lead trial investigator Thomas Louie, MD, of the University of Calgary said in a company press release. "The findings of this study support CRS3123 as such a candidate for further development."

Crestone also announced that, based on the results of the trial, the National Institute of Allergy and Infectious Diseases will provide $4.5 million in new funding for microbiome analyses, manufacturing process optimization, and other phase 2 supporting studies.

Treatment of C. difficile infection remains in urgent need of agents that spare normal gut microbes, so they can reconstitute the microbiome and prevent further recurrences of CDI.

Targeting older adults with underlying health conditions—as opposed to the general population—for respiratory syncytial virus (RSV) vaccines would reduce spending and prevent illness, according to a modeling study yesterday in the Canadian Medical Association Journal (CMAJ).

The study compared the cost-effectiveness of different vaccine programs in different age groups with different medical risks. 

The model considered a population of 100,000 people aged 50 years and older. Vaccine characteristics were based on RSV vaccines authorized in Canada as of May 2024, with vaccine protection assumed to last 2 years. 

The cost-effectiveness threshold was $50,000 per quality-adjusted life year (QALY).

Optimal in oldest adults with underlying conditions

According to the study authors, without vaccination, they projected 131,389 (95% credible interval [CrI], 120,070 to 143,581) medically attended RSV cases, 12,068 (95% CrI, 10,324 to 13,883) hospital admissions, and 1,015 (95% CrI, 617 to 1,450) deaths annually among Canadians aged 60 years and older.

Vaccinating strategies based on age plus risk for RSV-related complications were projected to avert a median of 20% to 31% of outpatient cases, 38% to 42% of hospital cases, and 39% to 42% of deaths, the authors said.  Vaccines were most cost-effective, according to the model, when given to adults ages 70 and older, with one or more chronic medical condition.

We found that vaccination of older adults may be less costly and more effective than no vaccination.

"We found that vaccination of older adults may be less costly and more effective than no vaccination and that vaccinating people aged 70 years and older with chronic medical conditions is likely to be cost-effective based on commonly used cost-effectiveness thresholds," said Ashleigh Tuite, PhD from the Public Health Agency of Canada in a CMAJ press release.

"Strategies focused on adults with underlying medical conditions that place them at increased risk of RSV disease are more likely to be cost-effective than general age-based strategies," Tuite added. 

A study of 1.8 million adults published in JAMA Network Open suggests that—except for a slightly higher risk of inflammatory bowel disease and blistering skin disorders in a subgroup hospitalized for SARS-CoV-2 Omicron variant infection—Delta or Omicron BA.1 or BA.2 infection in highly vaccinated adults doesn't significantly raise the long-term risk of autoimmune diseases.

Led by investigators from the National Centre for Infectious Diseases in Singapore, the study team used the SARS-CoV-2 registry and a healthcare claims database to compare the long-term risk of new autoimmune diseases after Delta or Omicron BA.1 or BA.2 infection in recipients of COVID-19 vaccines and boosters with that in uninfected controls. The study period was September 2021 to March 2022, with a 300-day follow-up.

Of all participants, 27.2% had COVID-19, 72.8% were controls, 51.9% were women, and the average age was 49 years.

"Studies have reported increased risk of autoimmune sequelae after SARS-CoV-2 infection," the researchers wrote. "However, risk may potentially be attenuated by milder Omicron (B.1.1.529) variant infection and availability of booster vaccination."

Boosters may lower risk of new autoimmune disease

During Delta predominance, 104,179 participants had COVID-19 infections and 666,575 were controls, while 375,903 and 619,379 controls, respectively were infected during Omicron predominance. A total of 81.1% of infected participants had completed the primary two-dose COVID-19 mRNA vaccine series amid the Delta era, and 74.6% received boosters during the Omicron period.

Continued surveillance for autoimmune conditions arising after COVID-19 is still necessary during the Omicron variant era.

A significantly higher risk of 12 studied autoimmune diseases wasn't observed during the Delta or Omicron periods, except for inflammatory bowel disease (adjusted hazard ratio [aHR], 2.23) and bullous (blistering) skin disorders (aHR, 4.88) in hospitalized COVID-19 patients amid Omicron. An elevated risk of vasculitis was documented in vaccinated Omicron patients (aHR, 5.74) but not those who received boosters.

The study authors concluded, "Continued surveillance for autoimmune conditions arising after COVID-19 is still necessary during the Omicron variant era."