Thread by @hildabast

Away we go. J&J ENSEMBLE trial evaluation has landed - 8am again - thanks, FDA! ....1/n
fda.gov/advisory-commi…

...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: absolutelymaybe.plos.org/2021/02/21/a-r…)

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