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We have a lot riding on the Moderna COVID vaccine, but little insight into how it’s performing in trials. Tiny peek under the hood from their investor press release here: (1/10) https://investors.modernatx.com/news-releases/news-release-details/moderna-highlights-opportunity-mrna-vaccines-its-first-vaccines
In the “first-in-human” study for a vaccine, typically you start the first group of volunteers at the lowest dose, wait a short period of time, and assess whether it appears safe. Then escalate the dose a bit for the next group. (2/10)
In this case, Moderna reports that they’ve made it through that process and are now giving the highest dose to the final group. From this you know that there haven’t been any safety issues so far. Encouraging. (3/10)
You can’t however tell whether it’s working. In this study they’ll likely be testing to see whether vaccine promoted humoral (antibody) and cellular immunity. Antibody measurement is faster because the assays are easy. They’ll probably measure serially for several months. (4/10)
This means that in the coming weeks Moderna will start to learn whether volunteers develop antibodies and how strong the response is. Cellular assays take longer because they are complex, but that rounds out the picture. (5/10)
One (bad) possibility is that the vaccine doesn’t induce robust immunogenicity, in which case it might be scrapped immediately. Not great, as most other candidates are further behind. More likely it induces some responses, hopefully strong. (6/10)
However you still don’t know how well the responses predict actual protection. For this there needs to be a clinical efficacy study: Give vaccine or placebo to volunteers, follow them for some period of time, and see how many get infected in each group. (7/10)
How long will that take? Tricky to say. Usually these studies are quite long but they will probably accelerate if possible, perhaps by giving it to a very high risk group (like HCW in an outbreak area) and seeing what the difference in infection rates is after a few weeks. (8/10)
I believe that’s why they’ve said they could potentially have some doses available for clinical use for HCW as soon as the fall. Supposedly manufacture is already scaling up so they may start treating high risk groups while bigger trials get going. (9/10)
If it works and is safe, eventually they roll it out for all. This requires a lot of things to go right! I haven’t even mentioned a bunch of major things that can go wrong. But it’s the best path we’re looking at. Personally I am really, really hoping they pull it off! (10/10)
Moderna CEO now on CNBC confirms that they’ll start Phase 2 prior to immunogenicity data being available, based on safety data alone. That saves a few weeks/months for sure. Then rapidly to Phase 3 as well.
CEO Bancel confirms we won’t have an approved vac before 2021, but says they’re working with regulators on whether access for high risk groups can be achieved in event of a fall recurrence of COVID spread.
Addressing lower efficacy in older patients: they’ll plan to go to even higher doses in the elderly to see if it boosts immunity. Common strategy but not always effective
Final note of extreme tea leaf-reading: he gave maybe a vague hint that they have some human immunogenicity data already. Fingers crossed. https://twitter.com/Harri8t/status/1250027335828586496?s=20
Interview is now up on the website. Bancel reports they'll have Phase 1 human immunogenicity data in "early summer", and Phase 2 will already be ongoing at that point. A lot of people are going to be anxiously awaiting those data. https://www.cnbc.com/video/2020/04/14/moderna-ceo-forecasts-2021-as-the-earliest-for-an-approved-covid-19-vaccine.html
