Derek Lowe writes a column in Science Translational Medicine each week that I have found to be informative and readable, and this week has provided a vaccine roundup at the end of December which I'll briefly summarize and comment on here.
We know that the two mRNA vaccines from Pfizer/BioNTech and Moderna have gotten emergency approval and their deployment has started in the USA and other places. As I have emphasized in previous blog posts, the USA only has secured enough doses right now for 150 to 200 million Americans which is not enough in and of itself to bring us to herd immunity and get the virus under control. Since it is not clear we can obtain more of these two vaccines in 2021, it is important for us to look to the other vaccines under development, with hope that one or more of them is proven safe and efficacious and can also be deployed in 2021. For some of these vaccines, Operation Warp Speed (OWS) has secured hundreds of millions of doses, so if even one or two of them work and are approved, we could have enough vaccine for the entire USA population in 2021.
Derek reports on the current status of some of the other vaccines that might be ready to evaluate for EUA soon:
He emphasized the big mistakes made by both partners that has led to a very messy situation, some of the details which I have pointed out and previously discussed. The bottom line is that the publicly released data fall far short of establishing efficacy, and
there has been repeated tweaking of dose and schedule that is not expected when at the confirmatory trial stage, and as we statisticians know this type of small sample subgroup analysis can easily yield false leads and makes one suspect a fishing expedition.
As a result, USA and European regulatory agencies have said they will not provide emergency authorization based on the current data. However, the UK has approved it for emergency use this week, seemingly motivated by desperation given the emergence of a new variant, recently dubbed VOC-202012/01, that has in a few months come to take over the UK. There is evidence that it is more transmissible than previous variants, so Lowe reasons that the UK figures that "something is better than nothing" and they had better get the vaccine out to counteract the increased spread they expect this variant will produce. While it does appear this variant has evolutionary advantages and is experiencing natural selection, the available evidence does not yet establish a causal link between the variant and increased transmission, so more data is needed before we can be certain -- I will highlight this in a future blog post.
Until I see more and better data from this vaccine, it is not clear to me whether it will be approved in the USA, or should be. Fortunately, there is a large, rigorous phase 3 study in the USA that includes many older individuals, unlike the previous trials for this vaccine, and it is nearly done accrual so we should see results in the next month. I hope the results from this trial are positive at which point an emergency use authorization would be appropriate, but from what I've seen I'm not holding my breath.
Johnson and Johnson:
Lowe points out that the large single-dose trial of this adenovirus vaccine candidate is nearly complete and should show results soon. If positive, the fact that this only requires a single dose would make it majorly impactful.
This recombinant-protein based vaccine is expected to have results from a large phase 3 trial in the UK in the next month or two, and a USA phase 3 just launched this week. Its relative ease to manufacture and store makes it potentially impactful if approved.
Gamaleya Research Institute (GRI, Russia):
Lowe mentions the press release earlier this month reporting their two-dose adenovirus vaccine, Sputnik V, demonstrated 91% efficacy and that a peer-reviewed publication will be available soon. There are reports of it being shipped to several countries in the world, and AstraZeneca has partnered with GRI and they together have registered a clinical trial involving a combination of these two vaccines.
CanSino (Tianjin, China):
While no data have been publicly reported yet, it is said their adenovirus vaccine Ad5 has trial results being submitted to the Mexican regulatory agency for possible approval.
Sinovac (Beijing, China):
This is an inactivated-virus vaccine that Lowe mentioned that has reported 91% efficacy, but only based on a small sample of ~1300 subjects so we need to wait to see more.
SinoPharm/Beijing Institute (China):
Lowe mentions that Phase 1/2 data from their inactivated virus vaccine has just been published in the Lancet, and they have announced that preliminary analysis of their phase 3 trial has found 79% efficacy. However, it is not clear when data will be released and details of the trials unknown.
Hopefully, some of these vaccine candidates will work out and be approved and available in 2021, but nothing is certain, so I continue to believe it is vitally important for us to distribute the vaccine doses on hand carefully and wisely until we are confident we will have sufficient supply to vaccinate the country in 2021.