Away we go. J&J ENSEMBLE trial evaluation has landed - 8am again - thanks, FDA! ....1/n…
...First up, yes, outcome measure was reasonably close to what we're used to. Here it is based on the FDA-harmonized definition (including mild disease) - & keep in mind this is with South Africa &c included: vaccine efficacy 67% (CI: 56-75) (CI is a measure of uncertainty)...2/n
...This is what that looks like. Keeping in mind it's a single shot - and 28 days after it is about similar to the time of 7 days after BNT-Pfizer's second shot (as they're 3 weeks apart). (ENSEMBLE-2 is underway to see a 2nd shot on day 57) ...3/n
...Severe/critical Covid-19: there's a cut-off date for determining which were severe (adjudication), so could change a bit. Efficacy: 85.4%
(CI 54 to 97) - less certain for aged 60+, with lower numbers: definitely high efficacy, not sure how high though ...4/n
...Hoping to see more later on how severely ill the people were, why they met those criteria. Here's hospitalization: 0 vaccinated people out of over 19,300 after 28 days. Numbers a bit small here. Range of uncertainty for all who tested positive at all: CI 31 to 100 ...5/n
...A post-hoc (unplanned) analysis, looking at hospitalization for who didn't have signs of a previous infection. The 2 vaccinated people hospitalized within 2 weeks were high risk for severe Covid-19...6/n
...7 people died of Covid-19, all in the placebo group, all at high risk of severe outcomes, all in South Africa. 💔

A reminder of the impact of a variant...7/n
... I think this is the first time this very important outcome has been reported for a Covid-19 vaccine trial: all-cause mortality. Wide CIs, so a lot of uncertainty, but 🤞 ... 8/n
...Asymptomatic infection: pic of caveats, not data, because many. They'll have more data over time. Testing for signs of past infection in blood of people who tested negative before vax. Combined that & PCR testing, efficacy against asymptomatic infection 74%
(CI 47 to 88)...9/n
...Vaccine efficacy against moderate/severe Covid-19 was higher in the US: 72% (CI 58 to 82) than Brazil (68%) or SA (64%): over 80% against severe/critical Covid-19 in all 3 countries ...10/n
...Sequencing isn't complete, so they don't have vaccine efficacy rates for variants yet. No one so far had the B.1.1.7 ("UK") or P.1 ("Brazil") variant, but SA is 67% sequenced & 95% were B.1.351 ("SA" variant)...11/n
...Now onto safety & adverse events (AEs). (Reminder I have a backgrounder about what this all means:…)

Like BNT-Pfizer, they have solicited AEs for the first week for a subset. Moderna had them for the whole trial ...12/n
...Any systemic solicited AE (not injection-related): 55% vax vs 35% placebo; severe <2% vs <1% (that's low). (For Moderna it was 83% vs 53% (bigger injection), 17% severe if previously negative). May be some small under-counting for J&J; FDA said won't make much difference..13/n
...So what were those systemic AEs? Headache, fatigue, myalgia (muscle aches & pains), fever. Severe: Fatigue, myalgia, fever. Rates were higher for younger people (which is so for all of them)...14/n
...Detailed data on duration - I don't think we've had that for any others yet at this level. It was about 2 days. Rates for longer than a week were under 2% & about the same as in the placebo group. On to safety next ...15/n
...Some serious adverse events (SAEs) in people with confounding risk factors, where they could not rule out vaccine involvement: thromboembolic events (clots) & tinnitus (all but one resolving). They considered some cases of hives/swelling as possibly vaccine-related...16/n
...The SAE that resulted in a hold on the trial was a 25-year-old man who had a transverse sinus thrombosis 21 days after vaccine: ultimately determined not to be caused by the vaccine....17/n
...Out of the unsolicited AEs, they considered some (uncommon) likely to be vaccine reactions: arthralgia (joint pain), peripheral neuropathy (numbness or similar in hands/feet); muscle weakness...18/n
...Rate of SAEs similar in vax & placebo groups. FDA judged 3 likely vax-related: 1 allergic reaction (not anaphylaxis); 1 pain from possible injection injury; 1 a severe reaction that resolved in 4 days; plus...19/n
...The FDA couldn't rule out 4 other SAEs, though not likely to be vaccine-related.

There was a reproductive toxicity study (rabbits), which found no problems.

FDA evaluators satisfied on safety & efficacy...20/21
...Single shot, rate of adverse events much lower than mRNAs; high protection from severe Covid-19 & hospitalization; medium-high efficacy against symptomatic disease & possibly asymptomatic; held up against "SA" variant; affordable & low vax costs, non-profit, distributable. /21

• • •

Missing some Tweet in this thread? You can try to force a refresh

Keep Current with Hilda Bastian, PhD

Hilda Bastian, PhD Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!


Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @hildabast

25 Feb
ca 600,000 vaccinated with BNT-Pfizer vaccine in Israel, matched on demographic/clinical characteristics of 600,000 unvaccinated (median age 45) showed results similar to the phase 3 trial... 1/n… Image
...Similar pattern, for infection, symptomatic Covid-19, hospitalization, severe disease, death: 10,561 people infected, 57% of them developed symptoms; 369 in hospital, 229 severe Covid-19, 41 deaths...2/n Image
...7 days after 2nd dose: 92% efficacy against infection (CI: 88 to 95) - that's a strong result. Hospitalization: 87% (CI: 55 to 100) - wide confidence intervals, so not so certain. Remember, it's a group on the young side...3/n
Read 5 tweets
24 Feb
It's another ENSEMBLE-watch day! The FDA meets on 26th to discuss the evaluation of the J&J single-shot vaccine - 3rd vaccine for FDA - & they aim to publish report 2 days ahead, which they achieved for the last 2. So 🤞 all will be revealed in a few hours ... 1/n
...This is where reports will be posted:…

Trial protocol:…

Press release with trial efficacy readout:…

My thread on it:

Records on this vaccine:… ...2/n
...Things I'll be watching out for. By far the biggest set of "events" (people with symptomatic Covid-19) of any trial. So it'll be the strongest data yet on questions past that top line efficacy - efficacy in severe disease, for example, which others had too few to answer ...3/n
Read 7 tweets
22 Feb
Report from Scotland with great news on Covid vaccination reducing hospitalization rates. Not enough data released to be sure about much beyond that though, & number of vaccinated people hospitalized appears to be too small (happily!) to draw much beyond that though...1/2
..Some details about the study… BBC says 58 people in hospital who were vaccinated a month before: % by vaccine & for over 80s, but that number seems too small to break it down it by vaccine & age. Overall, ca 90% lower. 🤞… 2/2
...Ah ... preprint tweeted by @jaclark73 - thanks!… Just hunting out the numbers now... 3/n
Read 18 tweets
19 Feb
This Oxford-AstraZeneca vaccine study from a preprint a couple of weeks ago is now published in the Lancet. At first look, there are some additions... 1/n…
...In the original thread, I'd had a question about hospital admissions, but ignore that if you re-read it: the wording is expanded a little in the paper, & it clears it up... 2/n
...The supplementary info includes listing of serious adverse events & unsolicited adverse events, but no data on solicited adverse events - all of that is new...3/n…
Read 5 tweets
18 Feb
EMA (Euro drug regulator) assessment report for the Oxford-AstraZeneca vaccine is online. This one's 181 pages. Most of it's based on the original November data (as in the Lancet publication) but some includes is Ded 7 data (as in recent preprint):… ...1/n
...They had a major objection to the US manufacturing plant (it's also manufactured in the UK & Belgium - EMA is not assessing Covishield, the Indian version, at all). However, their concerns were resolved. Sounds like it was missing certification...2/n
...EMA wants additional data to validate quality of manufacture at all 3 sites is comparable. Since there's no assessment of Covishield here & WHO didn't do it, I assume this rests totally on the Indian regulator, which published no data (Indian trial still unpublished)...3/n
Read 21 tweets
16 Feb
TGA (Australian drug regulator) issued 2-year provisional approval for the Oxford-AstraZeneca vaccine, no age restrictions, with a cop-out on age - pushing the onus onto individual decisions. 4 to 12 week interval… ...1/n
...The Public Assessment Report released with the decision (49 pages)… It's for the AstraZeneca version: when CSL (local producer) is ready to supply, that won't need new clinical data... 2/n
...Reproductive safety study in mice is still underway - not recommended for pregnant women before then. Under clinical data, raised issue of follow-up injections possibly decreasing immunity... 3/n Image
Read 9 tweets

Did Thread Reader help you today?

Support us! We are indie developers!

This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!

Follow Us on Twitter!