Massachusetts-based biotechnology company Moderna (NASDAQ: MRNA) has announced positive interim data from a phase 1 clinical trial of its mRNA vaccine against the coronavirus that causes COVID-19.
The phase 1 clinical trial involved the administration of vaccine at one of three doses (25, 100, and 250 micrograms) 28 days apart to 45 healthy adults and is being conducted by the National Institutes of Allergy and Infectious Diseases (NIAID), a branch of the National Institutes of Health (NIH).
- After receiving two doses of the mRNA-1273 vaccine, all participants in the 25 and 100 microgram dose cohorts developed binding antibody against the coronavirus at levels “at or above” those observed in the blood of recovered COVID-19 patients (‘convalescent sera’)
- Participants in the 25 and 100 microgram dose cohorts tested for neutralizing antibody were found to bear the protective antibody at levels “consistent” with those of mice protected from infection in a challenge model and “reaching or exceeding” those observed in convalescent sera
- The interim data from the phase 1 trial indicates that the vaccine is “generally” well tolerated and safe, with complications primarily occurring among participants that received the highest dose of vaccine (250 micrograms)
- A mouse challenge model demonstrated that the vaccine provided “full protection” against replication of the coronavirus in the lungs
- A phase 3 clinical trial of mRNA-1273 is expected to start in July of 2020
Across all three dose cohorts, participants were found to develop antibody against the coronavirus within 15 days of receiving a single dose of the vaccine. While individuals that received 25 microgram vaccine doses developed levels of anti-coronavirus binding antibody similar to those observed in the blood of recovered COVID-19 patients (‘convalescent sera’), participants in the 100 microgram dose cohort were found to have “significantly” higher binding antibody levels. According to Moderna, data from the 250 microgram group is not yet available.
The first four patients in the 25 and 100 microgram groups (eight total) were assessed for the presence of neutralizing antibody, antibody capable of effectively inhibiting replication of the coronavirus which is distinct from binding antibody, which binds to the virus but does not necessarily prevent infection. Plaque reduction neutralization (PRNT) assays demonstrated that all eight participants were found to have neutralizing antibodies “at or above levels generally seen in convalescent sera.”
According to Moderna, the interim phase 1 data suggests that the vaccine is “generally” safe and well tolerated, with only a few adverse events that were “transient and self-resolving” and no grade 4 or serious adverse events. Among participants in the 25 and 100 microgram dose cohorts, the only observed adverse event was grade 3 erythema, or redness, around the site of vaccine injection. “Systemic symptoms” after the administration of the second dose were observed in three individuals that received the 250 microgram dose of vaccine.
A viral challenge model that involved the deliberate exposure of mice vaccinated with mRNA-1273 to the SARS-CoV-2 virus demonstrated a lack of viral replication in the lungs, suggesting that the animals were protected from infection by the coronavirus. The mice were found to bear levels of neutralizing antibody “consistent” with those of the participants in the phase 1 clinical trial.
Based on the interim data from the phase 1 trial, the phase 2 study of mRNA-1273 will be modified to include two dose levels, 50 and 100 micrograms. According to Moderna, the phase 3 clinical trial will likely evaluate a dose between 25 and 100 micrograms and is expected to be intiated in July of 2020 “subject to finalization of the clinical trial protocol.”
Chief Medical Officer of Moderna Dr. Tal Zaks, MD, PhD, stated, “These interim Phase 1 data, while early, 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 µg. When combined with the success in preventing viral replication in the lungs of a pre-clinical challenge model at a dose that elicited similar levels of neutralizing antibodies, these data substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials.”
Moderna CEO Stéphane Bancel stated, “With today’s positive interim Phase 1 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 3 study in July and, if successful, file a BLA. We are investing to scale up manufacturing so we can maximize the number of doses we can produce to help protect as many people as we can from SARS-CoV-2.”