Barely a year since the emergence of the SARS-CoV-2 virus, multiple vaccine developers are poised to secure emergency authorization in the USA and the EU.
Pfizer and BioNTech’s BNT162b2 — an mRNA-based vaccine — was the first of the candidates to reach a final, event-driven efficacy analysis. The company reported on 18 November that a 43,000-patient phase III trial had reached 170 confirmed cases of COVID-19, with only 8 of these in the treatment arm. These findings equate to an efficacy rate of 95%. The company observed ten severe cases of COVID-19 in the trial, with only one of these in the treatment arm.
Severe adverse events included fatigue and headache following the second vaccine dose.
Moderna’s mRNA-vaccine mRNA-1273 offered 94% efficacy, showed a final analysis of their 30,000-patient phase III trial. Moderna’s trial accrued 196 cases of COVID-19, with just 11 of these in the treatment arm. The company observed 30 cases of severe COVID-19, none of which were in the treatment arm.
Common adverse reactions included injection site pain, fatigue and myalgia.
AstraZeneca has reported promising interim results for AZD1222, an adenovirus-based vaccine developed in partnership with Oxford University. As of 23 November, the company had observed 131 confirmed cases of COVID-19 in a pivotal trial of the vaccine. The average overall efficacy estimate is 70%. For subjects who accidentally received a half-dose of the vaccine at a first visit, followed by a full dose at a second, the estimated vaccine efficacy is 90%.
AstraZeneca’s results raised optimism that its vaccine supply could be stretched further, but also questions about why a lower dose may have worked better and concerns about how this dosing mistake was made.
The Russian Gamaleya Center’s Sputnik V vaccine, another adenovirus-based vaccine, offers an efficacy of 91%, showed an interim analysis. This estimate is based on 39 confirmed cases of SARS-CoV-2 infection.
As Nature Reviews Drug Discovery went to press, none of these findings had been published in peer-reviewed papers. Outstanding questions include the duration of the effect and the long-term safety of these vaccines. An FDA advisory panel will discuss the Emergency Use Authorization of Pfizer’s vaccine on 10 December, and of Moderna’s vaccine on 17 December.
The UK’s MHRA has authorized Pfizer’s vaccine for emergency use.
Other candidates in phase III trials include more traditional protein subunit vaccines and inactivated virus vaccines.
This pipeline is set to defy historic vaccine development timelines and success rates. The average time for a vaccine to move from phase II to licensure is 4.4 years, found a recent analysis of the development trajectories of 220 vaccines for viral diseases that were developed in 2005-2020. The average probability of progressing from phase II to licensure within 10 years was 10%.
Nature Reviews Drug Discovery 20, 8 (2021)