It has been all of 2 weeks since the company announced the 30 April Topline Data results and this forum has all but decayed into a tit for tat following the fall in share price. A series of posts up and down ramping misinformation, general chaos and a feeling of continued fearmongering resides.
This post contains my view on the 30 April announcement, that will oppose some of the other views put out there by other posters.
Is the company going to be sued ?You need to decide this one for yourself as anyone can 'try' to sue anyone for just about anything these days. Two things of interest on this subject came out of the webcast.
1. None of the analysts nor the company even gave any air time about the possibility of MSB getting sued for anything. This perhaps demonstrates how unimportant and insignificant the notion of a possible legal proceeding actually is, otherwise for sure the analysts would be asking the question if not the company providing an update on it's legal battles.
2. The disclaimer at the beginning of the call ( which takes up 5% of the call by the way ) quite clearly indicated that the call was only the companies beliefs on the 30April, which may differ from actual results and that the beliefs may change and the company is not obligated to tell anyone about the changes in belief. Good luck arguing any promises were made in a court of law with a disclaimer like that.
Remestemcel only works when used with Dexamethasone...or maybe it is actually the Dexamethasone that is providing the mortality reduction ?Dexamethasone was introduced as standard of care mid trial after the UK RECOVERY trial demonstrated approximately a 30% mortality reduction in ventilated patients when given Dexamethasone. In the case of the RECOVERY trail, dexamethasone 28 Day mortality went from 41% down to 29%. Source here
https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1 \
The big question is.... was the mortality in the RECOVERY trial in the UK, similar to the mortality for the mesoblast trial in the USA, and the answer is they really cannot be compared.
This is because Mesoblast released two stats for controls in the under 65's , both are for 60 days and they do not appear to replicate the RECOVERY data.
Mesoblast Mortality rate for control under 65's ( includes some people with and some without dexamethasone ) 42%
Mesoblast Mortality rate for control under 65's that includes all dexamethasone 45%.
Remarkably the Mesoblast trial data released actually shows that
dexamethasone slightly increased the mortality rate in the under 65 group !
So what did Remestemcel do ? It reduced mortality from 42-45%, all the way down to 14% if used with Dexamethasone, or 26% if used without dexamethasone, demonstrating the first traces of a significant mortality reduction for ventilated patients.
Will Vaccines make Remestemcel obsolete?This was effectively asked by Cantor Fitzgerald. Si mentioned that vaccines have observably reduced caseloads successfully, but in the context of evolving strains where vaccine effectiveness changes, along with expected pockets of disease as human to human contact increases when the world re-opens , a baseload of around 20% was being prepared for. Si mentioned the US current load sitting near 500,000 per year, and IF vaccines continued to be used and effective, 20% of that number, along with approximately 70,000 influenza ARDS patients were being planned for.
This would indicate the company scaleup is perhaps looking at 200,000 treatments of 2 doses for ARDS cases annually in the USA. Conservatively - taking a quarter of the 2015 Temcell average price in Japan per treatment ( because the treatment is a quarter of the GvHD regimen ) Each patients would be up for $35,000 USD or a Market revenue of 7 Billion USD.
Has the company discussed results with the FDA or US government ?The impression I am left with is definitely not. That is because Si " Very early days" " We only just unblinded the topline data ourselves" clearly mentioned that BARDA discussions are about manufacturing ramp up and that before they occur, the company needs agreement from the FDA. Before going to the FDA , the company needs to fully analyse all the secondary data etc, which has not occurred yet, and also consult with their partner Novartis - who have not even finished looking themselves.
The timeline I think for this will be something like May/June 2021 MSB and Novartis analyse the results with Novartis confirming the deal. Meeting with FDA then scheduled Q3 2021, and future all cause ARDS trial design.... or another COVID ARDS announced starting Q4 2021. Si questions how ' Robust is the data' and ' what level of confirmation is needed' ..... I think that is all pointing towards another trial with dexamethasone in under 65's and Novartis involved.
Can this result aid GvHD?MSB deliberately used the same dosing regimen as GvHD although for 1/4 as long since the condition is shorter. This supports the safety data, and has provided evidence of biologic activity in the under 65's with mortality reduction, but not in the over 65's. My take on the ARDS side - MSB think they will need another trial either to confirm the under 65's ARDS response, or change the treatment for over 65's to make it effective for everyone. Remember this point being raised in the GvHD..... why did it only work for children and not adults? it's the same disease.... now we have why is it only working in under 65's ? Will come down to if the FDA believe the under 65 data is sufficient, and if comorbidities are the reason. I think they get the jist of where the treatment is heading and how it could be used for multiple diseases, so are going to tread very carefully here.
It's possible if the biomarker data is good enough..... they might get a phase 4 approved - since they will have treatment effect in an adult population.
EUA?Comments from Fred and Si both point towards the signal detection work finding something very important. That we could be looking at the first real treatment to meaningfully reduce mortality significantly when used with dexamethasone, and that a meeting with the FDA had been setup because it is now warranted. However when balanced with the size of the trial, and robustness of the data ( only in under 65's ) it could just blend into the background with the FDA. Worst case do another trial in under 65's with dexamethasone. ( I think Novartis would welcome this )
Will the company treat Outside USA?SI
- The data will be applicable to submissions made outside the US, and " we will no doubt be performing additional studies with the same target population and same dosing regimen in combination with dexamethasone. Together with Novartis we will look at how to make this available in other areas..... clearly that is going to happen after Novartis sign, after the FDA meetings occurred, and I wouldn't expect movement in this are until probably Q4 - 21
It sounds like we are close..... we are so dam close, some will say they have heard all this before - but this time with a major partner onboard, phase 3 data to back it up and a worldwide pandemic causing mass death.
I think we are 1 short Covid trial away from entering the US market.
This is not financial advice....and always do your own research.
(20min delay)
