A Moderna messenger RNA vaccine for influenza now has preliminary data from a pivotal study showing the shot prompted a strong immune response to the more common strains of the virus but fell short against less common strains.
The results reported Thursday are from one of two pivotal studies for the Moderna vaccine, mRNA-1010, which is assessing the shot for safety and immune response. A separate Phase 3 study is evaluating the shot for efficacy. Results from that study could come as early as next month.
Moderna’s vaccine encodes hemagglutinin, a protein on the surface of the influenza virus that is also the main target of currently available flu shots. Two types of the virus, influenza A and influenza B, cause seasonal flu. The Cambridge, Massachusetts-based company designed this vaccine to address four strains recommended by the World Health Organization, two of them from the more common influenza A type and two from the less prevalent influenza B.
The clinical trial, conducted in the southern hemisphere, enrolled 6,102 adults who were randomly assigned to receive a single dose of either MRNA-1010 or an approved seasonal flu vaccine. The main goals were measuring the development of antibodies in the blood and determining the antibody response to viral infection. Against the two influenza A strains, the Moderna vaccine was superior to seasonal flu vaccine on the measure of antibodies. In the assessment of antibody response, the Moderna vaccine was superior against one of the influenza A strains and no worse than seasonal flu vaccines for the other. But against both influenza B strains, the Moderna vaccine was not able to beat seasonal flu vaccines for either trial endpoint.
Moderna acknowledged the vaccine’s shortfall against the influenza B strains. In a statement, Moderna President Stephen Hoge said that the company has updated the vaccine with changes that could improve the immune response against influenza B. He added that the company aims to assess those improvements in an upcoming clinical study.
On assessments of safety, Moderna reported that mRNA-1010 was well tolerated by patients. About 70% of patients who received the Moderna shot reported adverse reactions compared to 48% of study participants who received a seasonal flu vaccine. But most of the reactions were classified as low-grade and included pain, swelling, headache, muscle pain—the same kinds of reactions that people experience with seasonal flu shots. Moderna said the rate of adverse reactions was lower in older participants compared to younger ones.
The Phase 3 study assessing efficacy is being conducted in northern hemisphere countries. So far, the trial has accrued more than 200 cases confirmed by PCR testing. Moderna said that consistent with the dominant influenza strains circulating this season, more than 99% of these confirmed cases were caused by influenza A viruses. The independent data and safety monitoring board is expected to review data from an interim analysis by the end of March. Based on that review, the board will notify Moderna whether the main goal has been met or whether the study should continue.
The mRNA-1010 vaccine is one of five influenza vaccine candidates in Moderna’s pipeline. All of them include additional hemagglutinin antigens in order to achieve broader coverage of circulating strains. In addition to these shots, Moderna is also developing combination vaccines that could protect against multiple pathogens. A single shot that protects against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) is in Phase 1 testing; a combination vaccine for flu and RSV is also in Phase 1.