Thread by @DrEricDing

BREAKING—U.S. govt is considering giving some people half-dose of Moderna's #COVID19 vaccine in order to speed vaccinations, says Moncef Slaoui, head of Operation Warp Speed, in talks w/ FDA. Bold, but maybe possible—let’s walkthrough the trial data. 🧵
reuters.com/article/us-hea…

2) "We know that for the Moderna vaccine, giving half of the dose to people between the ages of 18 and 55, two doses, half the dose, which means exactly achieving the objective of immunizing double the number of people with the doses we have," Slaoui said.
#COVID19

3) “We know it induces identical immune response” to the full dose, he added.

...well, it is true that the full dose and half doses yielded roughly similar immune responses in Phase 1&2 trial/ of the vaccine. Though there are slight caveats. So let’s walk thru that data...

4) So the Phase 3 standard dose is 100 microgram (aka ug) of “mRNA-1273”—the designated name used in trial reports. There were 2 trials comparing the 50 vs 100 microgram versions:

📌Phase 1 trial of 15 people per dose regimen

📌Phase 2 trial of 185-189 people per dose regimen

5) First, the tiny Phase 1 trial with 15 people per arm: IgG antibody levels of spike protein recognizing antigen. Similar for 50 vs 100. Minor decline on day 57 but not sure if real. But no Day 119 comparison.

6) Next for viral neutralizing ability in Phase 1 — both 50 and 100 microgram doses again very similar. Though no day 119 in the phase 1 for the 50.

7) In the bigger Phase 2 study of antibody binding, it’s clear both 50 and 100 microgram much much better than placebo.

“GM fold-rise” is multiples of increase vs baseline, w/ 1x = same as baseline.

The 50 & 100 doses both good, w/ 50 ug achieving ~ 78-82% of 100 full dose.

8) Finally, the all important neutralizing antibody levels in Phase 2... both doses much better than placebo of course.

📌And at day 29, the 50 microgram half dose was 75% as high as the 100 ug full dose.

📌at days 43 & 57, after 2nd booster dose, the 50 and 100 ug were equal!

9) Conclusion—based on the (better/larger) Phase 2 dosing data, it seems the half dose 50 ug Moderna #COVID19 vaccine is about 75-80% as good as the full dose in the first month, ➡️ but once 2nd dose is delivered, neutralizing antibody levels are the same for half vs full dose!

10) That said, I wish we weren’t so supply chain strapped and stuck in such a raging pandemic that we have to ponder how to stretch our vaccine doses to more people this way. This reminds me of the deferred 2nd dose vaccine debate, which is tough discussion to be honest.

11) also this still has to be FDA approved of course in order for the half dose to be considered. They will be reviewing the same data I presented, available here: fda.gov/media/144452/d…

FDA could decide this pretty quickly I expect w/ another virtual expert meeting. #COVID19

12) A caveat is that the Phase 3 mega trial did not use the 50 ug dose, but rather the 100 ug. Thus, it’s imputing efficacy for #COVID19 prevention based on the neutralizing antibody data—akin to imputing heart attacks prevented based on LDL cholesterol lowering alone. 🤔

13) from the above data, is it safe to infer that 50 ug dose would be similar to 100 ug after 2 doses based on equivalent neutralizing antibody levels from Phase 2? Unclear. Welcome @PeterHotez @florian_krammer @VirusesImmunity @michaelmina_lab @ashishkjha @RickABright thoughts.