COVID-19 vaccines shatter efficacy projections: Data Byte
With Moderna’s announcement Monday that its COVID-19 vaccine produced 94.5% protection in a Phase III trial, two mRNA vaccines have beaten their projected efficacy thresholds. The findings bode well both for other mRNA vaccines and for vaccines of other modalities that deliver the virus’ spike protein.
Release of the full Phase III protocols of leading COVID-19 vaccines made it clear the companies were aiming for at least 50% efficacy at final analysis, with higher performance needed to see statistical significance at earlier, interim analyses.
In the past two weeks, mRNA-1273 from Moderna Inc. (NASDAQ:MRNA) and BNT162b2 from BioNTech SE (NASDAQ:BNTX) and Pfizer Inc. (NYSE:PFE) both beat their projected efficacy thresholds by wide margins at interim analyses. The Russian Sputnik V vaccine, which is a viral vector vaccine rather than an mRNA vaccine, also produced over 90% efficacy, albeit at an earlier analysis with less data.
Together, the findings boost confidence in mRNA as a new vaccine modality and use of the SARS-CoV-2 spike protein as a powerful antigen.
Johnson & Johnson (NYSE:JNJ) and AstraZeneca plc (LSE:AZN; NASDAQ:AZN) both expect Phase III data by year-end from viral vector-based COVID-19 vaccines. J&J’s JNJ-78436735 encodes the spike in an adenovirus serotype 26 (Ad26) vector, which is one of two adenovirus vectors used in Sputnik V. AZ’s AZD1222, developed with the University of Oxford, uses a simian adenovirus vector dubbed ChAdOx1.
The chart compares interim efficacy data from BNT162b2, mRNA-1273 and Sputnik V versus the level of protection vaccine candidates need to show to be deemed effective at their planned interim and final analyses. Each analysis is set to occur at a specified number of PCR-confirmed COVID-19 illness events.
For AZD1222, efficacy must be 50% to meet the primary endpoint. At the single planned interim analysis, which is set to occur at 75 infection events (not shown), that would require a two-sided 99.7% CI >30%. At the final analysis, a two-sided 95.1% CI must be >30%.
For JNJ-78436735, monitoring of the primary endpoint begins, and continues as cases sequentially accrue, after four conditions are met: half the planned subjects have been followed for at least two months; and observation of at least six COVID-19 cases in a 60 and older cohort, 20 cases overall and five severe/critical cases. To meet during interim evaluation or at the targeted 154 events, vaccine efficacy must be at least 50% against severe/critical COVID-19 and >30% against moderate to severe/critical COVID-19.