Breakthrough! Coronavirus vaccine

FE and partner BNTX reported positive top line Ph3 data for its COVID-19 vaccine, BNT162b2. The trial met the primary endpoint (preventing COVID-19 in those without evidence of prior SARS-COv2 infection) and per the release the case split between vaccinated individuals and those who received the placebo indicates a vaccine efficacy rate above 90%, at seven days after the second dose. But as the study continues, the final vaccine efficacy percentage may vary. Per the release the DMC has not reported any serious safety concerns and recommends that the study continues to collect additional safety and efficacy data as planned.

The data will be discussed with regulatory authorities worldwide. No details are available at this point on secondary endpoints, such as impact on severe COVID-19. In our opinion the data should support an emergency use authorization (EUA) filing by the end of November, in line with PFE’s prior guidance. In our view this is a positive for PFE shares and bolsters our confidence in the outlook for other vaccine candidates in development. As we previewed (LINK) we believe a vaccine efficacy rate above a low end of ~60-65% will likely be viewed positively by investors. Dr Anthony Fauci (Director of NIAID) has said scientists are hoping for a vaccine that is at least 75% effective, but that 50% or 60% effective would be acceptable.

Pfizer/Biontec  announced that its COVID-19 vaccine achieved >90% vaccine efficacy in preventing COVID infections based upon the first interim efficacy analysis of 94 confirmed cases, conducted on Nov 8. The efficacy is stronger than anticipated. The PR stated that “after discussion with the FDA, the companies recently elected to drop the 32-case interim analysis and conduct the first interim analysis at a minimum of 62 cases. Upon the conclusion of those discussions, the evaluable case count reached 94 and the DMC performed its first analysis on all cases.”

Pfizer plans to submit Emergency Use Authorization (EUA) in the third week of Nov, after the 2-month median safety milestone is achieved. We look forward to tolerability and safety details, which have not yet been disclosed. The trial will continue through a final analysis at 164 confirmed cases. The trial has enrolled 43,538 participants to date, and of these, 38,955 had received a second dose as of Nov 8.

PR noted that there will be a new secondary endpoint evaluating efficacy based on cases accruing 14 days after the second dose. Pfizer expects to produce 50M vaccine doses in 2020 and up to 1.3B doses in 2021.

One important thing to note is that vaccine, if rolled out, will have to be kept at below minus 80 degrees. That may mean good news for companies such as €68bn French listed Air Liquide and $1.1bn US listed Belief Solutions both of whom specialise it keeping things that need to be cold, cold. (There will be others, but those spring to mind initially.)

Some questions remain, but at this stage of the trial, this is a nearly unmitigated win. Pfizer and other companies were assuming a vaccine efficacy of 60% – these data clearly outperformed and are about as good a result as could be hoped at this stage. Notably, the interim analysis included more than half of the events needed for the final analysis, lending greater confidence that the >90% efficacy will hold relatively steady.

Safety is more of a question both because Pfizer provided no details in its release, and because longer follow-up is required. Still, signs of antibody-dependent enhancement would potentially have emerged by now, so we are not out of the woods on safety but are at least headed in the right direction. This win also greatly increases the likelihood that competitor vaccine candidates will be successful – wonderful news for society.

Risks to success of BNT162b2 remain, and include: 1) there could be a reduction in efficacy with continued follow-up; 2) the vaccine could protect from symptomatic infection, but do a worse job at protecting from severe disease in vulnerable populations, 3) the vaccine could do a worse job at protecting against some new, common variant of the virus, and 4) rare and/or time- delayed safety concerns could emerge.

SVB Leerink says the disclosure is very promising and that importantly the 90 per cent efficacy was based on a substantially larger number of interim cases than the previously planned 32 cases. In terms of when to expect the vaccine’s availability, they say Christmas is possible target (our emphasis):

Pfizer and Biontech reiterated that they should be able to file for an EUA by the 3rd week of November. At this stage, the likelihood of a major safety issue emerging is relatively low. After more than 38,000 individuals have been given the second dose of the vaccine, and observed now for at least 7 days, the risk of serious safety events, that might halt the program, is likely to be low. This means that Pfizer is likely to get their EUA by early December, and can then proceed to label and distribute the vaccine in the middle of December, with initial vaccinations being administered to high risk individuals by Christmas. Pfizer’s supply is likely to be limited through the first quarter of 2021, and then to ramp up quickly, and other vaccine companies are also likely to have their products available by late Q1 or Q2 next year.

Meanwhile, other data to expect from the trial is as follows:

Pfizer and Biontech confirmed that they are continuing to accumulate safety and efficacy data from the trial and will have the full 164 events for the final efficacy analysis relatively soon (not surprising given emerging infection rates around the world). This additional observation will increase the safety data base and should easily surpass the FDA’s minimum two months of safety observation for 50% of the study enrolment. This additional data should also allow the sponsors to accumulate safety beyond the initial 7-day observation period, and to accumulate evidence for efficacy against severe COVID disease, as well as to

show efficacy in a variety of racial and demographic subgroups, and in individuals previously exposed to the virus. All of these will alleviate many of the concerns expressed by participants in the recent FDA advisory committee meeting (see our note HERE), and potentially contribute to faster uptake of the vaccine (as it becomes available).

There is a non-linear relationship between efficacy and the vaccination coverage required for herd immunity: the higher efficacy, the lower the herd immunity threshold. Assuming an R0 of 2.5, 90% efficacy implies that governments would need to reach vaccination coverage of about 60% to reach herd immunity. This should be feasible over the course of 2021.

They’re also bullish about the source being Pfizer, arguing that, relative to other candidates, access to this vaccine will be far broader:

Most governments in advanced economies have pre-ordered a significant number of doses; in per-capita terms the US, the EU, Canada, Japan, the UK, Australia and New Zealand have all pre-ordered enough doses to take a major step toward herd immunity early next year. In EM, governments have not ordered as much, having put more of their eggs in the AstraZeneca basket. Still, Pfizer’s competitive pricing means that many EM governments will be able to purchase significant numbers of doses into next year.

And on sterling:

Most clearly, GBP is a major beneficiary, not only because the UK government has good exposure to Pfizer in its broad and deep vaccine portfolio, but also because the UK has perhaps struggled the most with managing the pandemic without a vaccine. In other words, a vaccine could make the biggest difference to the economic outlook in the UK, relative to its peers in G10.

So, all in all, everyone is cautiously optimistic.