You Read it Here First Folks….With Opinion! Ozanimod and COVID-19

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The problem with some Pharma Science is it is just a list of facts…without opinion….Boring some may say:-).

They can’t give opinion because it may breach someones rules and so they can’t say “mine is bigger than yours”…at least in some countries. So they can say mine is this big and hope you know that yours is that big so that you can work out is whose is bigger. Put they only say that if their’s is bigger…..Some people don’t have the time to work it out….and just want to be told.

There are loads of different S1P1 modulators and the question is…..Are they all the same?…After all they can all inhibit relapsing MS.

COVID-19 came along and it could have been important as fingolimod was limited COVID-19 vaccine efficiency. Are they all the same?…We suggested No.

However it doesn’t take a rocket scientist to work out that they are not the same…….You can ask a student , who hadn’t done research before to look at the available information and their response is “They are not the same and this is maybe why”.

Next up. Dare you put your “neck on the line (block)” and make suggestions….We did this when COVID-19 came along. We did this in this instance too.

Dare you speculate what may happen in the future?…Get it wrong and you look a chump!

Speculation is kryponite (Superman hates it) or is it garlic (Vampiire Hate It) to some scientists, who mess their pants at the hint of speculation. If you don’t show it, it can’t be true….hence the pace of discovery is hampered as you can’t join dots. You can only say facts….Maybe these scientists have been reading pharma papers for too long:-)

Anyway after that light-hearted introduction.

I just have to give a shout out to Eugenia Forte, a visiting medical student who did the digging and the speculation as literature review for their project. They are not a Professor or an immunologist, yet but they suggested that fingolimod may be different from the other S1P modulators in relatation to SARS-Cov-2 vaccination and could give some suggestions. Ozanimod and ponesimod and siponimod may make a vaccine response, whereas fingolimod had a blunted T and B response. There was plenty of evidence for the results with fingolimod and when we made the suggestion not much evidence…however it trickled out in meeting reports and now in paper form

….Eugenia’s ideas answers what happens with ozanimod an S1P modulator, which I don’t think is available in England. I am not sure they could be bothered to be NICEd…Correct me if I am wrong..

Ozanimod does not stop the COVID-19 related vaccine response in general.

Cree BAC, Maddux R, Bar-Or A, Hartung HP, Kaur A, Brown E, Li Y, Hu Y, Sheffield JK, Silva D, Harris S. SARS-CoV-2 vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis. Ann Clin Transl Neurol. 2023 Aug 7. doi: 10.1002/acn3.51862. 

Objective: To investigate the serologic response, predictors of response, and clinical outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis (RMS) from DAYBREAK.

Results: In fully vaccinated participants (n = 148), spike RBD antibody seroconversion occurred in 90% (n = 98/109) of those without serologic evidence of prior SARS-CoV-2 exposure (100% [n = 80/80] seroconversion after mRNA vaccination) and in 100% (n = 39/39) of participants with serologic evidence of viral exposure. mRNA vaccination predicted higher spike RBD antibody levels, whereas absolute lymphocyte count (ALC), age, body mass index, and sex did not. COVID-19-related AEs were reported in 10% (n = 15/148) of fully vaccinated participants-all were nonserious and not severe; all participants recovered.

Interpretation: Most ozanimod-treated participants with RMS mounted a serologic response to SARS-CoV-2 vaccination and infection, regardless of participant characteristics or ALC levels. In this analysis, all COVID-19-related AEs post-full vaccination in participants taking ozanimod were nonserious and not severe.

This is open access have a read…but if you wonder why there is this difference?. It is Magic….To be fair they did give a Nod to an answer and referenced Eugenia’s paper without saying what is said so have a read of that too…a taylor made answer….

Baker D, Forte E, Pryce G, Kang AS, James LK, Giovannoni G, Schmierer K. The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination. Mult Scler Relat Disord. 2023 Jan;69:104425.

Published November 2022 and available online SSRN 6 September 2022 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4200732

This post is relevant because of the question posed below, when you look at fingolimod and CD20-depleted individuals who have a poor SARS-COV-2 response to viral and RNA vectors and suggests a possible response to a Protein vaccine in adjuvant as an alternative.

Mueller-Enz M, Woopen C, Katoul Al Rahbani G, Haase R, Dunsche M, Ziemssen T, Akgün K. NVX-CoV2373-induced T- and B-cellular immunity in immunosuppressed people with multiple sclerosis that failed to respond to mRNA and viral vector SARS-CoV-2 vaccines. Front Immunol. 2023 Jul 20;14:1081933. doi: 10.3389/fimmu.2023.1081933. 

The question one has think about is …….Do you change vaccine? or Is it easier to change drug to something that allows a better vaccine response?.

COI: None really

Disclaimer: My views and yes this is about Our paper and not the Cree paper….stick that up your altmetric and smoke it…..:-)

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