Vaccine failure blows a hole in Pfizer's pipeline

Burying the failure of a trial in bullet point number four of a press release is not typically a big pharma strategy. But perhaps desperate times call for desperate measures: Pfizer’s C difficile vaccine is considered one of its most valuable development projects, and the group is under pressure to beef up its pipeline. True, hopes had dimmed after the pandemic threatened to derail the 17,500-patient Clover trial, and Glaxo’s competing, earlier-stage programme ran into similar problems. Clover was designed on an assumption of 66 C diff cases within two years, but in the end Pfizer had to run the final analysis after 42 cases within four years of vaccination. No p values were disclosed for the two primary vaccine efficacy endpoints, but these yielded wide confidence intervals and must have failed by a considerable margin. And while the company highlighted secondary endpoints that appear to point to a reduction in severe disease and disease duration, regulators will surely struggle to consider those findings rigorous. Regulatory opinions will be sought, Pfizer said. Perhaps significant unmet need, previous failures that have demonstrated how tough this setting is, and a thin pipeline coming behind will act in the company’s favour.

The Clover trial – topline readouts 
  Vaccine Placebo
Co-primary endpoints 
1st primary episode of CDI ≥14 days after 3rd dose  VE = 31%
1st primary episode of CDI ≥14 days after 2nd dose VE = 27%
Selected secondary endpoints
Median CDI duration 1 day 4 days
Mean CDI duration 3 days 16 days
Number of participants seeking medical attention for CDI  0 11
Number of participants requiring medical attention (incl. hospitalisation) for CDI  0 17
VE= vaccine efficacy; CDI = C diff infection. Source: company press release. 

 

A poorly C diff vaccine pipeline 
Project Company Status
PF-06425090 Pfizer Ph3 Clover trial failed; company to discuss data with regulators
VLA84 Valneva Ph2 completed in 2015; further development dependent on partner
GSK2904545A (recombinant protein-adjuvanted vaccine) Glaxosmithkline Ph1 trial ongoing (work suspended in 2020 owing to pandemic) 
MVX02 Matrivax Research & Development Preclinical  
MV-001 MV Biotherapeutics Preclinical  
C diff vaccine  Sanofi Abandoned in 2017 after Cdiffense trial failed interim analysis
Source: Evaluate Pharma & company communications.

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