Moderna raises the bar for Covid-19 vaccine efficacy

The first pivotal results with Moderna’s mRNA-based Covid-19 vaccine look even better than those Biontech/Pfizer released a week ago.

A basic reading of today’s hotly awaited pivotal Covid-19 vaccine results from Moderna is that they have beaten those from Biontech/Pfizer. But in a global pandemic meeting initial demand will be a huge issue, so when it comes to vaccine successes the more the merrier is a good rule of thumb.

Curiously, the markets do not see it that way, with Moderna up 8% this morning and Biontech falling 11%. Both rival vaccines use mRNA, a modality that has never been available commercially; perhaps the most important point about the two datasets, therefore, is that they show that this approach could be a goer.

Already Biontech/Pfizer’s BNT162b2 had massively beaten expectations, last week showing greater than 90% efficacy in protecting people from Covid-19 infection versus placebo (Pfizer and Biontech snatch first Covid vaccine victory, November 9, 2020). The financial community had expected around 70% efficacy.

This morning Moderna raised the stakes, claiming a 94.5% figure at the first interim analysis of the Cove trial of mRNA-1273. The US FDA had set a 50% threshold to consider any project for early approval, and both assets have clearly beaten this.

Company Biontech/Pfizer Moderna
Project BNT162b2 mRNA-1273
Study NCT04368728 Cove
Target enrolment 43,538 30,000
Cases in active cohort 8* 5
Cases in placebo cohort 86* 95
Efficacy >90% 94.5%
Manufacturing capacity 2020 50m doses 20m doses
Manufacturing capacity 2021 1.3bn doses (250m in H1) 500m to 1bn doses
Note: *estimated. Source: company announcements & Evercore ISI.

Moderna’s interim analysis had been triggered by 53 cases of Covid-19 infection being reported in the 30,000-volunteer study, though because of rising coronavirus infection rates the actual number of cases adjudicated by the data-monitoring committee was 95.

The headline finding was that 90 of these occurred among control patients, versus just five in the mRNA-1273 cohort. Perhaps even more impressive, albeit with small numbers of patients, was the incidence of protocol-defined severe Covid-19 cases: 11 for control, and none with the investigational vaccine.

With global use being one aim of Covid-19 vaccination, safety is paramount, especially for a novel approach like mRNA. Moderna said there were no significant concerns in Cove, with severe events including injection site reactions, fatigue, myalgia, arthralgia and headache; most were short lived, though of course a long-term look is needed to give the full picture.

Like the Biontech/Pfizer study, Cove will continue until the final number of cases specified in the protocol (164 for BNT162b2 and 151 for mRNA-1273) are reported, though no doubt there will be calls for both trials to be unblinded to give placebo recipients the chance to get vaccinated.

Governments have already signed supply agreements for both of these and other Covid-19 projects, and several vaccines will likely be needed to meet initial demand.

Those T-cell responses

Scientifically minded investors will now want to see more detail about the nature of the responses that mRNA-1273 was able to elicit.

A notable difference had arisen between the two mRNA projects when they generated the first human data in phase I: both elicited strong production of neutralising antibodies, but only BNT162b2 could boast CD8+ (killer) T-cell responses to a meaningful degree (Covid-19 vaccine contest turns to T-cell responses, July 20, 2020).

Nothing is known so far about the nature of any T-cell responses in Cove, or about how these correlate with protection from infection. If mRNA-1273 has shown efficacy without a significant CD8+ T-cell response that could in itself be of interest; however, many view T cells as key to long-lasting immunity, and the durability of mRNA-1273’s protection will be closely watched.

While US emergency use authorisation is a priority to get a Covid-19 vaccine to those most at need, it should be noted that in the EU the regulator is already reviewing BNT162b2 and Astrazeneca’s AZD1222 under a special rolling procedure; today it announced that it was starting to evaluate mRNA-1273 too.

Attention now turns to the next pivotal Covid-19 vaccine readouts, from AZD1222, by the year end, and then from Johnson & Johnson’s Ad26.COV2-S. mRNA vaccines have set a high bar, and if these next two players’ more traditional approaches do not meet it expect them to play up attributes like ease of storage.

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