Pfizer-06425090 C Diff Vaccine Falls Short on Primary Endpoint

C difficile spores

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Clostridioides difficile infection (CDI) poses significant mortality risks and healthcare burdens. The phase 3 CLOVER trial assessed the detoxified toxin-A/B PF-06425090 vaccine for preventing CDI. Although the vaccine did not meet the primary endpoint of preventing CDI, it was found to be safe and well-tolerated, showing potential in reducing CDI symptom duration, medical attention needs, and antibiotic use.

In the study, 17 recipients of PF-06425090 and 25 placebo recipients experienced their first CDI episode 14 or more days after the third dose, resulting in a vaccine efficacy (VE) of 31% (96.4% CI: –38.7% to 66.6%). For the second dose, 24 PF-06425090 and 34 placebo recipients had their first CDI episode 14 or more days later, with a VE of 28.6% (96.4% CI: –28.4% to 61%). Although, the median duration of CDI was shorter with PF-06425090 (1 day) compared to placebo (4 days; P=.02).¹

The primary endpoints were the incidence of the first CDI episode occurring 14 or more days after the third dose (PD3) and the second dose (PD2). The study also evaluated CDI duration, the need for medical attention, and antibiotic use, along with the vaccine’s tolerability and safety.¹

Among participants with a first CDI episode, no PF-06425090 and 11 placebo recipients sought medical attention, indicating a post hoc estimated VE of 100% (95% CI: 59.6% to 100%). Similarly, no PF-06425090 and 10 placebo recipients required antibiotics, suggesting a VE of 100% (95% CI: 54.8% to 100%). Local reactions were more common with PF-06425090, but systemic events were similar between groups, with most being mild to moderate. Adverse event rates were comparable.¹

This Phase 3 observer-blinded study randomized 17,535 participants aged 50 and older, at increased risk for CDI, to receive either three doses of PF-06425090 or a placebo (administered at 0, 1, and 6 months).¹

This study follows a previous report from Contagion in 2022, where Pfizer announced that its investigational CDI vaccine, PF-06425090, did not meet the primary endpoint of preventing C difficile in the Phase 3 CLOVER trial. Although, vaccine efficacy for all CDI cases recorded 14 days post-dose 3 was 49%, 47%, and 31% at 12 and 24 months, respectively.²

In that report, the vaccine significantly reduced the duration of CDI episodes, with median duration dropping from 4 days to 1 day and mean duration from 16 days to 3 days. In the vaccine group, no participants required medical attention, compared to 11 out of 25 in the placebo group The trial involved approximately 17,500 adults aged 50 and older, randomized to receive either three doses of the vaccine or a placebo. Despite not meeting primary efficacy endpoints, the vaccine was well-tolerated and demonstrated a favorable safety profile. Some secondary endpoints remained unreported.²

Both studies indicate that while the PF-06425090 vaccine did not meet its primary endpoint, it reduced CDI duration and medical interventions. The vaccine was well-tolerated in both studies. Pfizer plans to evaluate the next steps in coordination with regulatory agencies.

References

1. Donskey C, Dubberke E, Klein N, et. al. CLOVER: A Phase 3 Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection, Clinical Infectious Diseases, 2024;, ciae410. Accessed August 27, 2024. https://doi.org/10.1093/cid/ciae410

2. Parkinson J. Pfizer’s C Difficile Vaccine Did Not Meet Endpoint for Phase 3 Study. Contagion. March 4, 2022. Accessed August 27, 2024. https://www.contagionlive.com/view/pfizer-s-c-difficile-vaccine-did-not-meet-endpoint-for-phase-3-study