Hi
@LeftYahooglad to see you're posting. My opinion hasn't changed since last week. I think we're closer than ever to success, despite what I see as a lack of clarity with terminology.
The thing that the FDA has
required in the CRL is
not a 'trial', as I read the ASX announcement.
It's '
further data'. This is Real World Data (RWD) that the FDA want to see - the kind that can generate Real World Evidence (RWE). There's no mention of a randomised, controlled trial.
In the ASX announcement, what MSB said it would do in response to the FDA requirement of further data was
not referred to as a trial, viz:
" ...
Mesoblast will conduct a targeted, controlledstudy in the highest-risk adults with the greatest mortality. This adult study is "
Each of the underlined words published by Mesoblast Ltd is critical IMO. As are the words not there.
CEO Itescu referred to it as a 'study' throughout the conference call. This makes sense to me i.e. a prospective, controlled study.
Not randomised.
Not placebo-controlled.
Then David Stanton, Jefferies, started talking about duration of an 'adult trial' & CEO Itescu went with that, making the point in passing that the anticipated duration was expected to be 'substantially less' than 18-24 months in duration.
John Hester, Bell Potter, then brought the Q&A discussion back to 'an additional study', and CEO Itescu talked about an 'adult program'. Then, for some reason which I can't explain, CEO Itescu then closed with a comment about an 'adult trial'.
So, which is it in your opinion? Trial? Study?
This image extract from John Colcato's article on the FDA's RWE perspective in the NEMJ may assist MSB stakeholders to come to grips with the issues as we now must wait for the 45-day Type A discussions:
I'll provide in a separate post some notes for HC readers on the value of a nonrandomised interventional study. In that post I'll differentiate between the value - from an FDA perspective - in a retrospective observational cohort study, as announced by Prof Kurtzberg - see
https://www.onclive.com/view/dr-kurtzberg-on-long-term-os-for-remestemcel-l-in-pediatric-steroid-refractory-agvhd - , and the value to be had even from a nonrandomised interventional study in a single-group trial with an external control group derived from RWD.
IMO we'll also now deal with that pesky legacy concern at the manner of selection of the null hypothesis in GVHD-001.
Sure, there's a short delay for MSB. But the FDA will get some fresh,
prospective RWE, it can tick its 'pivotal' approval boxes for first-in-field therapies, it can delay having to deal with the flood of biologics a little longer, it has more time to get proper funding for its biologics licensing review/ administration & it can do all this without killing the company (maybe). So, everyone's a winner folks.
Except the children.
Who have to wait a bit longer. And that's still, essentially, on the FDA (IMO).
MSB is still looking good, from where I'm sitting. Please don't panic folks. DYOR and don't simply believe or accept the opinions you are reading here now (including mine).
Cheers, and GLTAH
(20min delay)