Will Prof G have to eat his proverbial hat?
I have been telling people that an effective SARS-CoV-2 vaccine is a long way away and that we shouldn’t expect a commercially available vaccine for another 12-18 months. Maybe I am wrong. The Moderna phase 1 results were published by the NEJM yesterday and are more impressive than I expected. These results are so important because the vaccine is based on RNA technology, which is relatively easy to scale-up in terms of production, unlike recombinant protein vaccines or inactivated viral vaccines. Therefore this vaccine may be with us before the end of the year.
The Moderna RNA vaccine carries the code for S-2P antigen, consisting of the SARS-CoV-2 glycoprotein. The vaccine is given as two doses (Day 1 and Day 29) into the deltoid or shoulder muscle. The RNA then uses the molecular machinery of the deltoid muscle to make the immunogen that then stimulates the immune response to the antigen, which will hopefully prevent wild-type SARS-CoV-2 infection and prevent COVID-19.
This has potential implications for how we treat MS. It increases the likelihood of a successful vaccine to prevent COVID-19 and increases the chances of pwMS having to be vaccine-ready in a 6-9 month time scale rather than a 12-18 months period. Clearly this has implications for how we manage patients on DMTs that have been shown to blunt or prevent protective vaccine responses, in particular, pwMS on anti-CD20 therapy (rituximab, ocrelizumab, ofatumumab) or S1P-modulators (fingolimod, siponimod, ozanimod, ponesimod).
Will Prof G have to eat humble pie or his hat? The market response to the data below suggests he will. What will be the implications for the MS DMT market? I suspect an effective coronavirus vaccine will hit the anti-CD20 market the most, which means ofatumumab’s MS launch will be a damp squib.
Jackson et al. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. NEJM July 14, 2020 DOI:10.1056/NEJMoa2022483
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.
METHODS: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.
RESULTS: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.
CONCLUSIONS: The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461
CoI: multiple