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.

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."

• The North Carolina Department of Health and Human Services yesterday reported the state’s first measles case since 2018. In a statement, health officials said the patient is a child in Mecklenburg County who was probably exposed during international travel. The parents kept the child home after returning to the state, except for one medical visit during which health providers took appropriate precautions. Cases in the United States are up sharply this year, part of a global rise in cases.
• The US Centers for Disease Control and Prevention (CDC) last week in an update that it projects that vaccine manufacturers will supply the US market with 148 million flu vaccine doses for the 2024-2025 season, with trivalent (three-strain) vaccine making up all formulations. Vaccine makers aren’t reporting any manufacturing delays, the CDC said. Nearly all (94%) of the supply will be thimerosal-free, and about 80% will be made using egg-based manufacturing technology. For comparison, the CDC had projected as many as 156.2 million to 170 million for the 2023-2024 season. It emphasized that projections may change as the season progresses.
• A polio vaccination campaign under way in Gaza has now moved to the northern part of the country, with activities slated to last until September 12, World Health Organization (WHO) Director-General Tedros Adhanom Ghebreyesus, PhD, said today on X. He called on groups in the region to maintain a humanitarian pause and respect the safety of healthcare workers. Following the recent detection of circulating vaccine-derived poliovirus type 2 in a child from Gaza, along with environmental positives, health groups planned and launched a two-round vaccine campaign earlier this month targeting 640,000 children.