I want to unpack a little bit the view of the FDA that's been thrown around on these boards, and I'm using Stockrock's words here because they neatly convey what you see in many posts after the FDA decision:
"With a positive light on the situation, some are looking at this as if the FDA is encouraging MSB to go down the path of accelerated approval. I outlined why I thought they would be doing that i.e. unwilling to make the leap to full approval and efficacy sign off on a single arm study, but basically covering their back side if it turns out Ryoncil doesn't work.
The opposite view of the situation is that there are some people in the FDA (or outside of the FDA) who do not want this treatment made available and/or delaying it as much as possible. In which case those in power and influence within the agency could very well stand their ground and throw the rule book at MSB at this Type A meeting and simply say that you missed your opportunity for accelerated approval and that in pursing such a path would be seen as undermining the entire FDA approval process. In which case, MSB either walk away.. or conduct that adult study prior to approval.
In many of the threads here you see this written about the FDA/Big Pharma, that they have it in for Mesoblast and MSCs somehow or that they are actively blocking the technology from reaching the market to preserve "big pharma monopoly".
Does this seem reasonable? Likely? No.
This is dangerous thinking and plainly wrong. If big pharma was so scared of Mesoblast and MSCs that they were willing to bribe government officials against the approval pathways for one product, it would be a huge costly risk. It would be much cheaper and more profitable to just buy Mesoblast and the technology. If they were convinced it would put all of big pharma out of business, one of the big companies would just buy Mesoblast and destroy all their competition. They're not doing that because there is no conspiracy against MSCs (though there is some skepticism).
What is happening though, is that there is a lack of trust in the new treatment. It's really new and different compared to your standard drug approval (this was mentioned regularly in the ODAC committee responses to the presentations) and it has no history or precedent from which the FDA can work from to ensure safety for patients. The FDA have to look at and understand and approve many many products each year, so they simply don't have time to become armchair experts in MSCs, the burden of proof is on Mesoblast, and being scientists and government, they have some strict requirements that must be followed in order to gain approval. Unfortunately, many of their policies use words like "shows a robust level of..." and "conforming to best practices in"... which are somewhat open to interpretation, and scientists are conservative people normally, they adhere to principles of robust scientific process to prove effectiveness. Mesoblast is a little more cavalier and took a practical view on this trial that a single arm would be enough.
So my view/summary of the timeline (and some opinions on why):
- FDA/Mesoblast agreed that they couldn't really do a randomised control trial on kids because it would mean intentionally killing some kids
- FDA looked at the situation, the trial, the history of the product, the newness of the therapy and decided that they shouldn't approve such a crazy new product without at least one successful RCT (also some other stuff on the biomarkers which is probably less important to them, but still they wanted it addressed). This is an ass-covering exercise so that if anything happens in the future there's not a trial where an FDA employee has to explain why they approved a treatment that hadn't even passed an RCT.
- FDA put strong concerns to the ODAC committee and expected the ODAC committee to recommend further trials
- The ODAC committee surprisingly recommended approval after some very convincing presentations and testimonies, but the FDA rep voted no. This is the practical choice in action (saving lives), which is a little bit at odds with the ass-covering or legalistic choice (we do it the right way, no matter what!).
- The FDA issued the CRL response and re-cited the need for a randomised control trial (as well as the biomarker stuff and maybe other things we are not privvy to)
Since NONE of us can see the full contents of the CRL, there's very little you can learn about what might happen in that type A meeting from HC posters. We don't know anything about the CRL other than what Mesoblast told us. To be fair, what they reported was in line with the FDA submission to the ODAC committee, but we have to assume that the upcoming meeting (if granted) will be a very unknown entity in the approval process, and there's no precedence to rely on because the FDA has already departed from precedence by ignoring the ODAC committee recommendation.
For all the skimmers, start reading here!
Which brings me to a long winded conclusion... DYOR, but for me, the FDA don't look like they will approve the GVHD product without an RCT, they may overturn that decision at the meeting (MSB think they will) but in my opinion the evidence suggests that they won't (the FDA member on the ODAC committee voted no despite hearing the presentations, they've consistently harped on about RCTs). It's not because they are lizard men or in cahoots with big pharma, they're just a bunch of cautious scientists that want to keep their jobs and cover their asses.
So for me now, it's all about Covid. They co-designed the trial, it has extra power at the FDA's request, it is a full RCT, the trial is enrolling at a good rate and this is the gold star evidence they can hold up to cover their asses and start approving MSC products. If I was Mesoblast I'd see the covid trial through to the full 300 patients (no early efficacy) and just get that to market and use it as a foot in the door for GVHD, CHF, LBP etc. Should be much less scrutiny on the other products once the first approval is gained.
I would love to be surprised by an approval after the meeting in the next 30 days, of course!
Did not think about that...at...all!!!?
(20min delay)