This morning brought news from Moderna of the very first human results from trials of their closely-watched mRNA vaccine candidate (mRNA-1273) against the coronavirus. Here’s Stat on the news, and here’s Endpts – the results can be summed up pretty quickly, because it’s all just at the press-release level to start with.
The trial was dosing volunteers in Phase I at three levels 25 micrograms, 100 micrograms, and 250 micrograms of the mRNA species. First off, immunogenicity (whether or not these doses caused people to produce antibodies). The good news there is that every participant at every dose level began producing antibodies (in other words, they “seroconverted) by day 15 after the first injection. The actual amount of antibodies produced went up in the higher-dosage group, and for the 25 and 100 µg folks, it went up after the second “booster” shot of mRNA as well. (The high-dose 250 µg voluteers seem to have maxed out after the first shot, actually).
That’s promising on the relative amounts of antibodies: everyone responded, and the response was dose-dependent (both in amount and across time, with the booster shot). As for a comparison to the outside world, the company says that the lowest-dose (25 µg) cohort (15 people), two weeks after the second dose, showed levels of binding antibodies that are the same as seen in the blood of people who have recovered from the coronavirus on their own, as tested in the same assay. And the medium-dose group (ten people), tested at the same time, showed antibody levels that “significantly exceeded” the levels seen in recovered patients. The company says that it doesn’t have the numbers yet for the rest of the trial participants; presumably we’ll be seeing those soon.
Now that’s good, but it only measures binding antibodies. What you want are neutralizing antibodies, ones that not only bind but do so in a way that shuts down the virus entirely (background here). Moderna says that they only have data to this level on the first four participants in the 25 µg and 100 µg groups, but the good news is that those results are consistent with the overall binding antibody numbers: all of these people developed true neutralizing antibodies, and the company says that these were “at or above” the levels generally seen in the blood of recovered coronavirus patients.
What about safety and tolerability? There were no adverse reactions in the lowest dose group, and one in the middle 100 microgram group – a so-called grade 3 erythema (redness) at the site of injection. In the high-dose group, there were three participants with systemic reactions, and the company doesn’t go into the details, but those would generally be fever, flu-like symptoms, perhaps body rash. All of these resolved themselves, the release says, and it mentions that there were no serious reactions. That’s important – as you might guess, the language here is pretty precise. “Serious” is a regulatory term, meaning hospitalization, perhaps permanent damage, etc., as opposed to “severe” which is a broader term (and which Moderna doesn’t use in their press release at all, either).
So these results have led to some clarity on the Phase II trials, as they should. The 250 microgram dose is being dropped – it seems to be more than is needed, with a greater chance of adverse reactions. The company is now going with 50 and 100 microgram dosing, and the 50 microgram dose is going to be tried out under these Phase I protocols right now. The Phase II trials should be starting soon, and the plan is to use that data to narrow down on a single dose for going into Phase III, which is now set to start in July. That will be somewhere below 100 µg; we’ll see how the Phase II pans out.
Now if you read the post here earlier this morning, you’ll wonder about how the Moderna vaccine compares to the Oxford and SinoVac ones. We don’t know: Moderna hasn’t run a rhesus monkey challenge test, and as you can see from that post, even when two different organizations have done that there’s still plenty of arguing room. What Moderna has done is a mouse challenge, also mentioned for the first time in today’s press release. All we have is that “vaccination with mRNA-1273 prevented viral replication in the lungs of animals challenged with SARS-CoV-2“. No further data on the dosage, challenge method and amounts of virus, etc., but they say that the amounts of neutralizing antibodies seen in the mice is consistent with the human results.
I’d characterize today’s results overall as “limited but promising”, and in other words, so far, so good. This is what you’d expect to see from a vaccine that works, and although it looks that way we don’t have enough information yet to quite say that it works, or how well. That is what Phase II and Phase III trials are for, and waiting for those results, from Moderna and from everyone else, will make the latter part of the summer and the fall interesting indeed. Won’t it, now?