Pfizer’s C. Difficile Vaccine Misses Primary Endpoint in Trial

Pfizer recently announced that a Clostridioides difficile (C. difficile) vaccine candidate did not meet its primary endpoint of C. difficile infection (CDI) prevention, but was 100- percent effective in preventing medically attended CDI and reduced overall severity.

The Phase 3 CLOVER trial enrolled nearly 17,500 adults 50 years of age and older. The study initially expected to accrue 66 cases of CDI within two years, but the COVID-19 pandemic forced the final analysis to perform at 42 cases within four years.

The primary efficacy endpoints of the trial were first primary episode of CDI less than 14 days following completion of the second dose. Vaccine efficacy under the primary endpoint was 31 percent following the third dose and 28.6 percent following the second dose.

Vaccine efficacy rose to 49 percent, 47 percent, and 31 percent up to 12 months, 24 months, and at the final analysis, respectively, for all CDI cases recorded 14 days post-dose three.

Additionally, the mean CDI duration was three versus 16 days comparing vaccine to placebo, corresponding to an 80- percent reduction in disease episode. TheTHe vaccine was well-tolerated and showed a favorable safety profile in all participants overall.

“We are encouraged by the promising potential benefit observed against more severe C. difficile infection, as a large portion of cases lead to extended diarrhea episodes that can require hospitalization,” Kathrin U. Jansen, PhD, senior vice president and head of vaccine research & development at Pfizer, said in the announcement.

“We will evaluate next steps for our program in coordination with regulatory agencies. We are grateful to everyone who made the CLOVER study possible, including the study investigators and the trial participants for their contribution to this important research,” Jansen continued.

C. difficile infection is a bacterium that causes an infection of the large intestine. In 2017, there were nearly 223,900 cases of C.difficile in hospitalized patients and 12,800 deaths. The CDC classified the infection as an “urgent public health threat.”

Pfizer will continue to evaluate data from the CLOVER trial and determine next steps for its C. difficile vaccine program. The company also plans to submit trial results, including all secondary endpoints, at a future medical congress, and in a peer-reviewed scientific journal.