Moderna on Monday reported positive interim data from a Phase I study of its vaccine candidate against SARS-CoV-2, with results showing that mRNA-1273 elicited neutralising antibody titer levels in all eight initial participants in the low- and mid-dose cohorts, reaching or exceeding levels generally seen in convalescent sera. Shares in the company jumped as much as 24% on the news.
In the ongoing trial, which is being led by the National Institute of Allergy and Infectious Diseases (NIAID), subjects receive mRNA-1273 at a dose of either 25 mcg, 100 mcg or 250 mcg. Moderna noted that immunogenicity data are currently available for the 25-mcg and 100-mcg doses after two vaccinations, and at the 250 mcg level after one dose.
According to Moderna, dose-dependent increases in immunogenicity were seen across the 45 patients at the three dose levels, and between prime and boost within the 25-mcg and 100-mcg dose levels. The drugmaker added that all participants across the three dose levels seroconverted by day 15 after a single dose. Specifically, at day 43, two weeks following the second dose, at the 25-mcg dose level, levels of binding antibodies were at the levels seen in convalescent sera, while at the same timepoint in the 100-mcg cohort, levels of binding antibodies "significantly exceeded" that seen in convalescent sera.
Moderna added that neutralising antibody data are available for the first four participants in each of the 25-mcg and 100-mcg cohorts, with results showing that mRNA-1273 vaccination elicited neutralising antibodies in all eight of these participants. The levels of neutralising antibodies at day 43 were at or above levels generally seen in convalescent sera.
In addition, results showed that mRNA-1273 was generally safe and well tolerated, with Moderna noting that one person in the 100-mcg dose cohort experienced grade 3 erythema around the injection site. Meanwhile, at the 250-mcg dose level, three participants developed grade 3 systemic symptoms following their second vaccination.
Chief medical officer Tal Zaks noted that while the data are early, they "demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 mcg." Zaks remarked "I think the totality of science tells us that this is the right antigen and it should be protective," adding there's "a clear linear correlation between total binding antibodies and neutralising."
Moderna also reported in a viral challenge study in mice, vaccination with mRNA-1273 prevented viral replication in the lungs of animals challenged with SARS-CoV-2. The drugmaker added that neutralising titers seen in the Phase I trial at the 25 mcg and 100 mcg dose levels were consistent with neutralising titers that were protective in the mouse challenge model.
Moderna said that based on the interim data, the upcoming Phase II study, which was recently approved by the FDA, will be amended to investigate mRNA-1273 at doses of 50 mcg and 100 mcg, with the aim of selecting a dose for pivotal studies. The company suggested that the dose for the Phase III study is expected to be between 25 mcg and 100 mcg.
"With today's positive interim Phase I data and the positive data in the mouse challenge model, the Moderna team continues to focus on moving as fast as safely possible to start our pivotal Phase III study in July and, if successful, file a BLA," remarked CEO Stéphane Bancel.
Commenting on the latest findings, Goldman Sachs analyst Salveen Richter said he is positive on the results, raising his probability of success for mRNA-1273 from 70% to 75%.
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