In an attempt to have an objective debate over MSB's prospects, wanted to run through the main competition to MSB for COVID-19 treatment. Be grateful for any constructive criticism or advice.
Lets be clear, there will be no vaccine for at least 18 months (if even then). Moderna is supposedly the front runner and might be available by end of 2020....if it is proven successful. No vaccine to get us out of this pandemic before we either:
A: have herd immunity (thus nullifying need for vaccine to a degree) or
B: literally still in semi-lock-down and economic stagnation/ruin
So the best method in the mean time is of course a cure or treatment of associated illnesses or the virus (which in the best case scenario would then allow employment of herd immunity). Of the main candidates I see to rival Remestemcel-L:
Gilead's Remedisivir - fights viral overload, not the cytokine storm, possibly useful in early stage inhibiting virus, but doesn't combat effects on vital organs. More worryingly, it has questionable success rates and safety - particularly around kidney and liver failure from previous Ebola studies.
Fujifilm's Avigan - a broad-spectrum inhibitor of viral RNA polymerase, has shown questionable success in data so far and had known issues with subsequent birth defects after use.
Sanofi and Regeneron’s Kevzara - an arthritis drug designed to prevent such cytokine storms, questionable success again and only proven worthwhile in late stage patients.
Roches' Actemra - inhibits the IL-6 cytokine signalling, but this is just one very simple aspect of the biological process and STAT analyzed more than 500,000 side-effect reports on rheumatoid arthritis drugs, and found "clear evidence that the risks of heart attacks, strokes, heart failure, and other conditions were as high or higher for Actemra patients than for patients taking some competing drugs".
Eli Lilly's Barticinibare - a JAK inhibitor broadly block an enzyme that cytokines rely on for signalling. To borrow a phrase they are akin to firing a shotgun rather than a rifle, at the problem. They may too broadly effect the immune system at a time when it is already compromised.
Regeneron and various other companies are looking at monoclonal antibodies, which bind to the spike proteins of COVID-19 so it cannot enter into host receptor cells. It seems one of the most promising and least consequential treatments that perhaps is a competitive threat to MSB. They are expensive and are likely to take longer to develop and trial. Some monoclonal antibodies in the past have shown not insignificant side effects. Ultimately they are very expensive and unlike Remestemcel-L, would require the entire population treated like a vaccine.
To me the virtue of Remestemcel-L, like most stem-cells, is it replicates and amplify the body's natural processes of growth and repair processes, without dramatically blocking natural markers, processes or balances with unintended or unknown consequences. Per Mesoblasts release, Remestemcel-L down-regulates the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.I suspect Remestemcel-L will address scarring of the lungs, collagen repair, kidney, liver, heart and other non-ARDS associated organ issues caused by cytokine storms. Mesoblast stem-cells will, per the website, "play a central role in the maintenance, repair and regeneration of blood vessels through the secretion of growth factors which act on endothelial cells to promote blood vessel regeneration and function". They will also repair tissue in for example the "heart and brain where they facilitate endogenous tissue repair by mechanisms including promotion of survival and function of mature cells within a given tissue or of the endogenous stem cells with which they are associated in niches within these tissues".
It seems to me MSB's treatment will very quickly allow Physicians to prevent or treat critical patients, which in turn will allow authorities to loosen restrictions and herd immunity to prevail, with low rates of serious cases quickly treated and low mortality rates. Economically (compared to monoclonal antibodies) they would only require use for a minority of the population. Not to mention the application to some 40% of influenza related deaths associated with ARDS amongst others.
Grateful to hear any insightful comments to confirm or dispel the above.
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