If you are holding, worth while taking 30 minutes to listen to the companies webcast response online.
Click here for webcast
I found it beneficial to also to read the fragmented collective viewpoints of everyone in the Update on BLA thread, with a few major points overlooked in some views
1. DSMB for secondary analysis of Covid 19 ARDS will be early November, enrollment expected to complete in December
2. Heart failure readout estimated for release prior to or during the NOV13-15 Heart Failure online summit
3. Back Pain results are also due out prior to Dec
4. The 30 day type A FDA response is also likely to come out in November
Given we are now in October, it's looking more and more likely that November is going to be
the month of serious company news with massive company upside / downside possible
FDA CRL Extracts:
"The FDA recommended that Mesoblast conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD."
- Mesoblast are requesting immediate approval to sell the product over the next 30 days, and conduct the requested FDA trial post sales against adults. There is a chance of this happening, but given the FDA completely ignored the 9-1 ODAC vote my view is that they will continue ignoring the demonstrated efficacy in the absence of a placebo arm, and in their formed opinion msb needs the placebo arm in adults to prove it works better than placebo. Again the SP will dump further if this plan is rejected by the FDA - regardless of us having no change in the situation from present.
- The plus side is that Mesoblast was planning on doing this anyway, and it would expand their product market size to 4 times the size on approval, which would support a much higher share price $10 - 20 if demonstrated efficacy and approved for all GVHD.
- Are they likely to demonstrate efficacy in Adults..... The data from the slides in the OODAC meeting says yes.
- Page 58 of 127 Last paragraph of the page in the FDA briefing package is significant FDA Briefing note link
- I found two extremely important things here 1. That when looking at all the results across the trials with 495 patients total, Age, Severity and the TNFR1 level in the product all appeared to be linked to the 100 day overall survival. However - the data appeared like this because the later trials with the improved product only treated children with the worst grades of the disease, which would cause the statistics to appear to favor treating children, with the worse levels of disease, with the new product - which is exactly what they found when they added all the trials together ( As in Pediatric patients, the new process with higher TNFR1 and more severe patients gave a highest efficacy ). 2. That when looking at a single LOT number GVHD Grade and Age was not related to day 100 survival ( P = 0.3175 and P = 0.1697), but TNFR1 was highly associated P=0.0042.
- This suggests that the new process would work in adults and children alike, and in all other grades of disease B/C/D and be just as effective.
- The analysis was repeated again using another single lot number n=77 and the same effect was observed, TNFR1 linked with day 180 survival p=0.0027. So - the data supports the only link between survival and the patient group that was treated, to be the TNFR1 level and that is what will be proven in any follow on adult Trial. Maybe they will include Grade A and B in this trial too, and treat all patients ( not just SR ) - because the initial trials which were undertaken to check efficacy with steroids, were with the older less effective product.
"The FDA also identified a need for further scientific rationale to demonstrate the relationship of potency measurements to the product’s biologic activity. Assays measuring the potency of remestemcel-L will continue to be refined to provide further scientific rationale for its use in severe inflammatory diseases with high mortality risk, such as SR-aGVHD and COVID-19 ARDS."
- I believe that the company here may look at the COVID results which will correlate TNFR1 levels with reduction in the tracked biomarker levels in the adult age bracket, along with providing further evidence on the effectiveness of the TNFR1 relationship and patient outcomes in the follow on GvHD trial - which appears to be the main concern the FDA has. Ie - why does it only work in children when it's the same disease in adults and doesn't work. We know the answer to this is that most adults were treated with the old process which had lower TNFR1 levels. So for them to use the same assays, but now show efficacy across grades and ages in the disease will be sufficient in my opinion to demonstrate the TNFR1 link to MOA.
- They may have had other assays they were considering in manufacturing, but the proof and correlation between TNFR1 and successful outcomes in the new process is high, so I'm of the opinion that expanding the patient target group and showing continued efficacy using the established process should be enough to answer the concern here. They basically cannot argue with results.
(20min delay)