Company hopes to start phase III trial in July

The Dow surged 900 points on news that Moderna’s Covid-19 vaccine — mRNA-1273 — showed promise in small phase I, open-label, dose ranging trial led by the National Institue of Allergy and Infectious Diseases (NIAID).

There are 45 people age 18-55 enrolled in the trial (males and non-pregnant females) and the company reported immunogenicity data for the three cohorts — the 25 μg and 100 μg dose cohorts, in which participants received two doses by day 43, and one dose in the 250 μg cohort.

“All participants ages 18-55 (n=15 per cohort) across all three dose levels seroconverted by day 15 after a single dose,” Moderna reported in a statement. “At day 43, two weeks following the second dose, at the 25 µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from Covid-19) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera. Samples are not yet available for remaining participants.”

What sent the markets soaring was the neutralizing antibody data, available for eight trial participants — four in the 25 μg cohort and four in the 100 μg cohort — that appears to show the vaccine’s potential to confer immunity. “Consistent with the binding antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in all eight of these participants, as measured by plaque reduction neutralization (PRNT) assays against live SARS-CoV-2. The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera,” the company reported.

The phase I trial looked at safety and tolerability and found that, in the 25 μg and 100 μg dose cohorts, there was only one grade 3 adverse event — erythema around the injection site. For the 250 μg dose cohort, three participants had grade 3 systemic symptoms after the second dose. All adverse events self-resolved, Moderna reported.

Along with the human study is a pre-clinical viral challenge study in mice.

“In this study, vaccination with mRNA-1273 prevented viral replication in the lungs of animals challenged with SARS-CoV-2,” Moderna reported. “Neutralizing titers in Phase 1 clinical trial participants at the 25 µg and 100 µg dose levels were consistent with neutralizing titers that were protective in the mouse challenge model.”

Moderna is slated to begin its phase II study with the presentation of the phase I safety data, and is expected to begin a phase III study once the phase II data become available, “subject to finalization of the clinical trial protocol,” Moderna noted in a presentation of the trial data so far.

During the press briefing, Moderna spokespersons said the biggest challenge the company is facing is whether it will get enough cases to demonstrate the vaccine’s efficacy. Demonstrating efficacy requires a robust placebo arm and a circulating virus against which to test it.

In a statement, Moderna said that, based on the data it has thus far, the phase II study “will be amended to study two dose levels, 50 µg and 100 µg, with the aim of selecting a dose for pivotal studies.” Moreover, the statement explained that the phase I study will also be amended to include a 50 µg dose level cohort. The company expects to start a phase III trial in July, subject to finalization of the clinical trial protocol. For the phase III trial, it plans to recruit 600 participants age 18 – 55 and 300 participants older than 55.

Candace Hoffmann, Managing Editor, BreakingMED™

Cat ID: 190

Topic ID: 79,190,791,932,570,730,933,190,926,192,561,927,151,928,925,934