Moving Forward: Investigational C Diff Vaccine, Therapeutics Headline Conference

This morning marked the start of the its 9th Annual International C Diff Conference and Health EXPO. After the program introductions, oral sessions were presented.

In the session titled, Development of a Vaccine with the Potential to Prevent Clostridioides difficile Infection (CDI), Jennifer Moisi, vice president, Global Tick-Borne Diseases and Enteric Vaccines Medical Lead, Pfizer, presented on the company’s investigational C difficile vaccine.

Moisi said the vaccine is a bivalent toxoid vaccine candidate that aims to preserve important antigenic epitopes to induce broadly neutralizing antibodies.

In the company’s first randomized study, there was a 3:1 ratio of patients receiving the QS-21 adjuvanted toxoid vaccine to 100 μg QS-21–containing C difficile vaccine or placebo. The vaccine was given in a shortened-month (0, 1, 3) or day (1, 8, 30) regimens.

The second study involved patients randomized in a 3:3:1 ratio to receive either 100 or 200 μg unadjuvanted C difficile vaccine formulation or placebo in stages 1 and 2 (sentinel cohorts of different age groups), and 3:1 to receive the selected dose of unadjuvanted C difficile vaccine formulation or placebo in Stage 3 (days 1, 8, 30).

The investigators sought primary outcomes of safety for both study. They also determined immunogenicity by measuring serum toxin A—and B—specific neutralizing antibodies.

The vaccine is currently being evaluated in its CLOVER phase 3 trial. This is an international study across 397 sites in 23 countries. Their subject enrollment is 17,536, and they expect results in the coming months.

In the session titled, The Burden of Clostridioides difficile Infection In the COVID-19 Era, Nicola Petrosillo, MD, head Infection Control and Infectious Disease Service, University Hospital Campus Bio-Medico, Rome, Italy, discussed the incidence rates in hospitals pre and post-COVID-19 periods.

Specifically there were no significant increases in the national quarterly SIRs for CDI for any quarter in 2020 compared to 2019. And the national CDI SIR steadily declined in 2019-Q1—2019-Q4 from 0.63 to 0.55 and remained stable at 0.52 for each quarter in 2020.

Petrosillo said precautions and increased training on PPE to prevent COVID-19 might have led to a reductions in C difficile. And this may have been particularly important for reducing transmission of C Diff spores which are often resistant to alcohol-based hand sanitizer.

Another theory is that clinicians were so focused on COVID-19, that less patients underwent CDI testing. While it remains to be seen what the exact factors were in reducing CDI, infection prevention control measures certainly played a role and could continue to work, the presenter said.

In the session titled, Results from ECOSPOR III, a Phase 3 Placebo-Controlled Trial of SER-109, an Investigational Microbiome Therapeutic to Reduce Recurrence of Clostridioides difficile Infection, Barbara McGovern, MD, vice president Medical Affairs, Seres Therapeutics discussed studies around this oral therapeutic.

SER-109 is a first-in-class investigational microbiome therapeutic, administered orally following antibiotics, to reduce recurrence of C diff. The pharmacokinetics of it show that SER-109 spores germinate into metabolically-active bacteria that colonize the GI tract, a process called engraftment. And engraftment induces broad compositional and functional changes associated with a clinical response.

SER-109 met phase 3 primary endpoint, showing a highly statistically significant 30.2% absolute reduction in the rate of C. difficile infection recurrence compared to placebo, according to studies. “SER-109 was more favorable to outcomes to placebo,” McGovern said.

SER-109 also had a safety profile comparable to placebo.