Moderna today presented Phase I data showing that its closely-watched messenger RNA (mRNA) COVID-19 vaccine candidate mRNA-1273 showed immunogenicity in patients 55 years old and older that was roughly the same or higher than data seen in younger patients at the dosage the company is using in its Phase III trial.
Moderna’s series of two 100 mcg doses of mRNA-1273 seroconverted all 120 participants in a Phase I trial (NCT04283461) after the first dose given on Day 1, with the area under the curve for all age groups exceeding the median of convalescent sera, Jacqueline M. Miller, MD, FAAP, Moderna’s senior VP of infectious disease development, stated during a presentation at the August meeting of the CDC Advisory Committee on Immunization Practices (ACIP).
The presentation included Moderna’s first release of detailed data on mRNA-1273 in patients older than age 55.
After the second dose was administered on Day 29, S-2P binding antibodies were seen in all age groups at levels equivalent to high-titer convalescent sera, Miller added. Moderna also reported geometric mean titer (GMT) levels of 267 for the 18–55 year old cohort, 324 for the 56–70 year old cohort, and 242 for the age 71-and-older cohort, compared to a previously published GMT of 109 in the convalescent sera.
mRNA-1273 was shown to induce CD4+ T-cells of the Th-1 phenotype 14 days after the second dose was given. Th1-biased CD4+ T-cell response was seen across all age groups, as were rare Th2 phenotype responses, Miller and Moderna added.
The new data has not been published in a peer-reviewed journal.
However, on July 14, researchers from Moderna and its clinical research partners published additional, mostly positive data in The New England Journal of Medicine (NEJM) from their interim analysis of the Phase I study showing that mRNA-1273 induced rapid and strong immune responses against SARS-CoV-2.
The findings published in NEJM were based on data through Day 57 across three dose levels (25, 100, 250 µg) in 45 healthy adults ages 18–55 years—15 adults in each dose cohort.
mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA vaccine encoding for a prefusion stabilized form of the Spike (S) protein. mRNA-1273 is one of 18 “Front Runner” candidates among the nearly 300 COVID-19 therapeutics included in GEN’s updated “COVID-19 Drug & Vaccine Candidate Tracker.”
The U.S. government has committed up to $2.5 billion toward mRNA-1273, including up to $1.525 billion toward manufacturing and delivering 100 million doses of the vaccine, through Operation Warp Speed, the program through which President Donald Trump’s administration has committed the nation to delivering 300 million vaccine doses protecting against SARS-CoV-2 by January 2021.
Mani Foroohar, MD, a senior research analyst and managing director, genetic medicines with SVB Leerink, wrote in an investor note that the data was consistent with expectations based on data from prior cohorts.
“We already reflect higher penetration into elderly/high-risk populations in our SARS-CoV-2 market model, so we see limited incremental fundamental impact from these disclosures and leave our estimates unchanged at this time,” Foroohar wrote.
Investors reacted to today’s data disclosure by sending Moderna shares up 6.4% to $70.50 at the close of trading, up $4.25 from Tuesday’s close of $66.25.
Foroohar added that he expected investor focus for Moderna stock to increasingly center on the upcoming release of interim data from the Phase III COVE trial (NCT04470427), which the company is conducting with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), as well as the commercial dynamics of pricing strategy and share split compared with large pharma competitors.
The COVE trial, an approximately 30,000-patient study launched in July, is designed to evaluate the safety of mRNA-1273 in 30,000 adult volunteers who do not have COVID-19. Participants will receive two intramuscular injections approximately 28 days apart. Participants will be randomly assigned 1:1 to receive either two 100 µg injections of mRNA-1273 or two shots of a saline placebo.
COVE’s primary endpoint will be the prevention of symptomatic COVID-19 disease. Key secondary endpoints include prevention of severe COVID-19 disease, as defined by the need for hospitalization), and prevention of infection by SARS-CoV-2.
Moderna is also studying mRNA-1273 in a NIAID-led Phase II trial (NCT04283461) designed to assess the safety, reactogenicity, and immunogenicity of two vaccinations given 28 days apart. The placebo-controlled, dose-confirmation study has enrolled a total 600 healthy participants across two cohorts: 300 adults ages 18–55 years, and 300 adults ages 55 years and up. Participants are assigned to placebo, a 50 μg, or a 100 μg dose at both vaccinations, and will be followed through 12 months after the second vaccination.
The Phase II study was “active, not recruiting” patients as of the most recent update July 17 on ClinicalTrials.gov.
