Moderna Announces Publication in The New England Journal of Medicine of Interim Results From Phase 1 Study of Its mRNA Vaccine Against COVID-19 (mRNA-1273).
Bull (Optimist) Summary: Highly encouraging results in a well-respected peer-reviewed biomedical journal. Impressive that mRNA-1273 elicited an antibody response in all 45 subjects tested, and neutralizing antibodies after the 2 dose regimen, especially at the mid-dose (100 ug) and high-dose (250 ug) (See footnote @ below for the key results paragraph from the NEJM paper), with antibody responses that appeared similar to convalescent serum. The safety profile looked acceptable, especially at the lower doses, with the 100 ug (and possibly a future 50 ug dose) providing a good balance of safety and efficacy. The vaccine was developed with proof of efficacy and acceptable safety in humans with amazing speed compared to traditional vaccine development.
Bear (Pessimist) Summary: It's very early days for mRNA-1273 with data from only 45 relatively young, healthy volunteers and only after less than 2 months (57 days). Efficacy data is in laboratory antibody tests with no data on actual clinical data on protection of humans against coronavirus-SARS2 infection, and 2 doses appear to be required. There were some safety signals that need to be analyzed more closely in future trials, including 1 patient at the lowest dose who didn't receive a second dose because of severe hives that developed on their legs, fever after the second dose in many patients, and a troubling response in one patient at the 250 ug dose (See footnote @@), which may occur even in the 100 dose in larger studies with more subjects, especially those that are most are most at risk for COVID complications. After all, when assessing the potential of a vacine candidate against a virus that will be administered in healthy people, safety is a huge consideration. Finally, the neutralizing antibody activity may bedecreasing quickly after the second dose (see footnote @@@).
Amp Summary (from scientific viewpoint): It's tricky at this point. We see the optimistic and pessimistic cases above, and feel a little bit of both. It's really good that the mRNA vaccine drove an antibody response, including neutralizing antibody activity at levels at least shortly after the 2nd dose, that appear relatively high. Furthermore, MRNA's speed at getting to this point in clinical development of a vaccine against a novel target is pretty amazing. However, there were safety signals and the success of this vaccine in getting adoption by a large percent of the population is still a very open question. This will require careful analysis of safety results from much larger and longer-term trials. Will the safety signal seen in 1 of the 15 high dose patients, which would be unacceptable if it is more than an extremely remote possibility, show up in lower dose (100ug or 50 ug) in much larger trials future? Even if it doesn't, what percent of the population will comply and take 2 doses of a vaccine that even in young healthy people, will likely give them one or more of mild or moderate chills, headache, muscle pain, fever, redness and pain on injection (See Table S2 of Supplement of NEJM publication (link below)?
Amp Summary (from Investor): We are biopharma value investors, especially in companies between $200M and $2B market cap. At around $30B market cap, MRNA is much larger than companies we target , and with no vaccine or therapeutic past a Phase 2 Clinical trial (even with Covid starting Phase 3 soon), we have not researched the numerous earlier phase vaccines and therapeutics to justify their very high market cap. Thus, we are not MRNA investors and do not have an opinion on its current valuation other than the above general comments.
Interim analysis of original cohorts of Phase 1 study evaluated two-dose vaccination schedule of mRNA-1273 across three dose levels (25, 100, 250 µg) in 45 healthy adults ages 18-55 years.
Neutralizing antibody titers were observed in 100% of evaluated participants; at the 100 µg dose level selected for Phase 3, the geometric mean titers were above those seen in convalescent sera
Vaccination with mRNA-1273 elicited Th1-biased CD4 T cell responses
mRNA-1273 was generally safe and well-tolerated
@Noteworthy efficacy paragraph from Results:
The mRNA-1273 vaccine was immunogenic, inducing robust binding antibody responses to both full-length S-2P and receptor-binding domain in all participants after the first vaccination in a time- and dose-dependent fashion. Commensurately high neutralizing antibody responses were also elicited in a dose-dependent fashion. Seroconversion was rapid for binding antibodies, occurring within 2 weeks after the first vaccination, but pseudovirus neutralizing activity was low before the second vaccination, which supports the need for a two-dose vaccination schedule. It is important to note that both binding and neutralizing antibody titers induced by the two-dose schedule were similar to those found in convalescent serum specimens. However, interpretation of the significance of those comparisons must account for the variability in Covid-19 convalescent antibody titers according to factors such as patient age, disease severity, and time since disease onset and for the number of samples in the panel
@Safety report from 1 250 ug patient
@@@ Neutralizing Antibody graph
The New England Journal of Medicine:
Author: Henry@Amp with additions by Manny@Amp