Reuters reported a sharp selloff in the biotech’s shares following the presentation of the results on December 10.
mRNA-1010 encodes for the hemagglutinin (HA) protein from four seasonal flu viruses based on World Health Organization (WHO) recommendations, including seasonal flu A/H1N1, A/H3N2 and influenza B/Yamagata- and B/Victoria-lineages.
In the Phase 1 trial, mRNA-1010 was evaluated at 50 µg (0.05 mg), 100 µg and 200 µg dose levels in younger adults (age 18-49) and older adults (age 50+).
The company said the data showed that the flu shot successfully boosted hemagglutination inhibition (HAI) assay geometric mean titers (GMTs) against all strains 29 days after vaccination at all doses tested in both younger and older adults, even at the lowest dose. And no significant safety concerns were observed, it added.
In its review of the data, Moderna outlined how its ultimate goal is to develop an annual pan-respiratory single dose booster vaccine that can be tailored to circulating strains of SARS-CoV-2, seasonal influenza and RSV.
“The positive interim results from our Phase 1 quadrivalent flu vaccine candidate, mRNA-1010, are an important milestone toward achieving that goal. It is encouraging to see that participants in the study who received the 50 µg dose, including older adults, achieved robust increases in geometric mean antibody titers against H1N1 and H3N2, the strains responsible for the vast majority of morbidity and mortality in this age group,” said Moderna CEO, Stéphane Bancel.
However, Jefferies analyst, Michael Yee, in a client note, said the results of the Phase 1 study showed the mRNA based shot's efficacy was on par, generally, with standard flu vaccines from Sanofi. "On one hand, the antibodies increased to good levels, but on the other hand, the levels aren't necessarily seen as high or necessarily better than some high-(effectiveness) vaccines such as Flublok or Fluzone."
Phase 2 study
mRNA-1010 may show similar immunogenicity as current enhanced flu vaccines, but there is potential for even lower doses to show similarly strong immunogenicity and testing of an even lower dose will take place as part of a Phase 2 study, which is now fully enrolled, stressed Moderna.
Interim analysis data from that trial is expected in early 2022 and could prove key as the study will include head-to-head evaluation of mRNA-1010 with a commercially licensed standard dose vaccine, said Bancel on a call on Friday with analysts. Preparation for a Phase 3 study of mRNA-1010 is also underway.
“Our view on mRNA-1010, from the beginning, is that we want to aim at being as good as the best enhanced vaccines in the market, those that achieve premium pricing for older adults, like Fluzone HD does, with the highest market share in the US, and we want to use that as the starting point from what we then go build off of in our overall flu franchise.”
The biotech’s strategy for seasonal flu vaccines is multifaceted, said the CEO.
Alongside the development of mRNA-1010, he said the firm's strategy involves a second pillar - the expansion of coverage beyond quadrivalent flu vaccines, with it looking to advance two new candidates - mRNA-1011 and mRNA-1012 - that offer the opportunity to broaden strain coverage and enhance tools available to public health authorities when selecting antigens.
A third pillar, which was previously announced, involves the widening of the immunologic breadth of its vaccines, including broader antigens – mRNA1020/1030 vaccines. “We will accomplish this by adding neuraminidase (NA) antigens, which have the potential to improve immunity by targeting more antigens that are more consistently conserved and subject to less antigenic drift over most years.”
The ultimate goal, though, is to pursue combinations: “We do believe that there is substantial value to be created by combining a very strong seasonal influenza vaccine platform, mRNA-1010, with COVID and eventually COVID plus RSV boosters,” said Bancel.
Tackling strain mismatch, vaccine efficacy issues
He anticipates such second and third generation product improvements will enhance vaccine efficacy and close some of the gaps from strain mismatch and other challenges in the flu market.
Currently approved vaccines are around 40-60% effective and face significant challenges from strain mismatch and antigenic drift, remarked Bancel.
And the CEO, zoning in on the H3N2 strain, during the call, reported how data from the past six years illustrates the co-circulation of multiple clades of H3N2 viruses each year, with the most common strain was different amongst many of the largest countries in the northern hemisphere.
“One of the challenges of the current vaccine regime is that a single clade is picked. Often, however, in the H3 category, it represents less than 40% of all circulating H3N2 viruses, creating a high likelihood of mismatch with vaccines in at least some countries. This, we think, represents one of the most significant opportunities for improving vaccine efficacy.”