Tomorrow, the FDA’s Vaccines and Related Biological Products Advisory Committee will meet and is widely expected to approve Johnson and Johnson’s (specifically Janssen Biotech, a subsidiary) single dose COVID-19 vaccine candidate. This will be the third vaccine available in the US. The company and the FDA have already released documents which show that the vaccine is safe and effective – although not as effective as the Pfizer/BioNTech and Moderna vaccines already approved.
The J&J vaccine was developed on a “replication-incompetent” (i.e. inactivated) adenovirus (common cold) platform which expresses the much discussed spike protein of the novel coronavirus. This is a well established methodology of vaccine development, unlike the mRNA platforms of Pfizer/BioNTech and Moderna. The specific adenovirus 26 platform has been used in vaccine trials for Zika, filovirus, HIV, HPV, malaria and RSV. Nearly 200,000 individuals have received vaccines from this platform. There are two major advantages to the J&J candidate: 1. It only requires standard refrigeration to maintain stability and 2. It is given as a single dose.
Before diving into its efficacy, there is one nuance to review from the clinical trial. For the J&J study, the primary endpoint was moderate and severe/critical COVID-19 illness identified by a patient prompted “illness visit.” This is slightly different from the Pfizer/BioNTech and Moderna endpoints which included mild illness – although severe illness was considered in a separate sub-analysis. This appears to be an intentional decision for, as I detail below, the J&J vaccine is significantly less effective in preventing symptomatic COVID-19 infection than vaccines currently available – but it is quite effective in preventing hospitalization and death from the disease.
As summed up by Dr. Brandon Dionne, assistant clinical professor in the School of Pharmacy at Northeastern:
“This is the challenge when we talk about efficacy. What endpoint are you using? For Johnson & Johnson, their definition was: How many people are diagnosed with symptomatic COVID-19? So even though the vaccine didn’t prevent symptomatic cases quite as well as the Moderna or Pfizer vaccines, it did a great job preventing hospitalizations and deaths.”
Overall, the J&J vaccine was 66.1% effective against laboratory confirmed, moderate to severe COVID-19 infections occurring two weeks after the first and only dose. By age, efficacy was essentially equivalent at 66.1% from 18-59 and 66.2% for those 60 and older. It was less effective in women (60.3%) as compared to men (69.8%). There were also striking regional differences with US showing 74% efficacy but South Africa at 64% and Brazil at 61%. Much press discussion has focused on the effect of the South African variant but I have seen no coherent discussion of the lowest efficacy in Brazil.
Additionally concerning, is that for those individuals with at least one comorbidity the vaccine efficacy was 58.6% as compared to those with no chronic conditions at 68.8%. For those with HIV the vaccine was only 47.5% effective, Hypertension 35.7% and Type 2 Diabetes 23.0%.
Similar to the Pfizer/BioNTech and Moderna vaccine, we again see a striking Kaplan-Meier plot showing a clear delineation between the placebo group and vaccinated group beginning between 2 and 3 weeks after inoculation (page 31 of https://www.fda.gov/media/146217/download).
Overall efficacy for severe cases was estimated to be 85% but this protective effect was more pronounced among the 18-59 years age group at 91.7%. For those 60 and older, the preventive efficacy was quite a bit lower at 70.3%. For hospitalization, the vaccine exerted a 93.1% efficacy after 2 weeks from inoculation. There were no deaths reported whatsoever in the vaccination group, all 7 deaths were in the placebo group.
Safety appears to be excellent. In fact there were fewer “medically attended adverse events” among the vaccination group (1.4%) than placebo (1.9%)
So what’s the bottom line then on this new candidate?
Clearly there is a much needed role for additional vaccines given the impossibly laborious rollout thus far. The J&J candidate has less rigorous storage requirements and can be given as a single dose. However, it lacks efficacy at key points – specifically when it comes to the South African variant, perhaps a Brazilian variant, among those that are older and those with key comorbidities (especially diabetes).
But we know from surge after surge that fewer cases in the population leads to fewer hospitalizations and fewer deaths. The J&J vaccine will be an invaluable tool at the population level but, from my perspective, should be directed towards those that are young and healthy, among whom it displays the greatest efficacy.