The FDA’s August authorization of omicron-busting booster vaccines from Pfizer-BioNTech and Moderna raised eyebrows because the decisions were based on animal studies. The lack of human data added another wrinkle to the increasingly stubborn COVID-19 vaccine market.
Now, Moderna is rounding out its case with results from testing its updated vaccine in people—and the data also vouches for the shot against an emerging coronavirus mutation, too. In a phase 2/3 trial of more than 500 adults, Moderna’s bivalent booster mRNA 1273.222 triggered a “significantly higher” immune response against the BA.4 and BA.5 omicron subvariants compared to an auxiliary dose of the company’s standard vaccine, mRNA-1273, which bears the commercial moniker Spikevax.
While the data “appear encouraging on first look,” there are several caveats surrounding the effectiveness of both Pfizer and Moderna’s re-tooled shots, according to a note from Bloomberg Intelligence, posted on Twitter.
Bloomberg Intelligence analyst Sam Fazeli flagged the fact that Moderna’s study “lack[s] disclosure of antibody titers for the control.” Fazeli also highlighted the fact that those given the bivalent booster had had their previous shot 9.5 months before versus 4.5 months for Spikevax. This gave the bivalent patients more time to “naturally develop more effective antibodies against BA.4/5.”
The results come shortly after Moderna published data in the New England Journal of Medicine showing a separate, BA.1-targeting bivalent vaccine—mRNA 1273.214—elicited a superior immune response against BA.1, BA.4 and BA.5 versus Spikevax classic, with that greater protection lasting at least three months.
Uncertainties aside, Moderna could certainly use the booster win. After a turbulent third quarter of production and safety “pain points,” the company in early November trimmed its annual sales forecast for Spikevax from $21 billion to a range of $18 billion to $19 billion. For the third three months of the year, Spikevax brought home $3.12 billion, below Wall Street’s expectations and down 35% from the same period in 2021.
Still, Moderna continues to hold out hope for a booster-fueled sales rebound in 2022’s fourth quarter. And while the extra two months it took Moderna to generate its in-human BA.4/5 results gave the virus more time to evolve, the company’s tweaked shot also appears to hold its own against the latest subvariant in the U.S.
In an assay-based exploratory analysis of 40 subjects, both of Moderna’s updated bivalent boosters charted “robust” neutralizing activity against the omicron descendent BQ.1.1, which is now the second-most prominent incarnation of the virus in the U.S. behind BA.5, according to the CDC. Still, the vaccines’ effects were notably diminished against BQ.1.1, with Moderna recording an approximately five-fold drop in titers versus BA.4/BA.5.
"Further study will be needed to confirm the findings in the preliminary analysis, but the initial results indicate robust neutralizing antibody response against BQ.1.1," a Moderna spokesperson said over email. "These data suggest mRNA-1273.222 may continue to provide superior protection against emerging COVID-19 variants including BQ.1.1. into the winter compared to the original Spikevax."
The fact that Moderna’s updated shot could continue to offer protection as the virus evolves might spur greater uptake of the boosters against COVID-19, which “remains a leading cause of hospitalization and death globally,” Moderna CEO Stéphane Bancel said in a statement.
"As a new variant of COVID-19 becomes dominant in the U.S., and other respiratory viruses co-circulate this winter, it will be more important than ever for vulnerable populations to get boosted to protect themselves from severe outcomes associated with COVID-19," the company's spokesperson said.
With regards to specific promotion plans in light of the data, Moderna's spokesperson said the company plans to share the results with global regulators and journals for peer review.
"We are also continuing to work closely with public health authorities to disseminate our data and encourage the general public to get boosted as we enter peak respiratory virus season," she added.
The company's comments come as use of the latest COVID-19 boosters in the U.S. remains stuck in the doldrums, with CDC data showing just 10% of people 5 years and older have received one of the updated shots.
Moderna and Pfizer both won FDA emergency nods for their updated shots this summer, though at the time, some critics took issue with the speed at which the prophylactics passed muster with regulators. A major point of contention had been whether the boosters should have been green-lit without data from human trials.
When giving the new shots its blessing in August, the FDA stressed it based the decisions on the "totality of available evidence," including the large body of data in the original COVID-19 shots, plus a clinical study in an earlier BA.1-targeted vaccine.
As for Moderna’s patchy third quarter, shortly after its booster rollout in September, the company came face to face with a supply holdup at an Indiana plant operated by its contract manufacturing partner Catalent.
“We had to deal with a very complex third quarter from a manufacturing standpoint—manufacturing not one product but two,” CEO Bancel told investors at the time. “We’ve had quite a number of pain points,” he added on an earnings call. “We are working through a lot of those issues.”
Adding to Moderna’s misfortunes, the journal of the American College of Cardiology this month concluded that the Boston-based biotech’s shot Spikevax carries a two-to-three times higher risk of myocarditis—or inflammation of the heart muscle—after a second dose versus Pfizer-BioNTech’s Comirnaty.
As for what 2023 may hold for it COVID vaccine business, Moderna is keeping its sales prophecy vague as it wrangles “a number of variables,” Moderna chief commercial officer Arpa Garay told investors earlier this month. Base case, accounting for signed contracts and supply deferrals from 2022, Moderna said it’s guaranteed to reach between $4.5 billion and $5.5 billion in 2023.
As those emergency supply deals gradually drying up, Moderna expects the COVID-19 vaccine market to mirror that for flu shots. The company has yet to lay out a potential price for its vaccine on the open market.
Pfizer, for its part, recently said it was weighing a private-market price between $110 and $130 per Comirnaty dose.
That price is not out of line with other vaccines that are provided to adults. It is more than what CVS, for example, charges for a flu shot ($50 or $95), but is less than many other vaccines including Pneumovax 23 ($141), hepatitis ($145), meningitis ($179), shingles ($205) and HPV ($261).