Mesoblast are in ongoing discussions with OTAT/CBER on their Ryoncil BLA re-submission. I found it intriguing that Silviu talked about an inspection of its Lonza facility, which he would only do if OTAT/CBER indicated that they would like to inspect it.
Not that its a sure thing, but if that is the case, then it tells me that OTAT/CBER are taking this resubmission seriously in that they agree with the MOA and are now assessing if theory has been put into practice by Mesoblast. This is an essential step for an approval of Ryoncil.
If Mesoblast can take care of manufacturing, and have the facility signed off (minor CMC items outstanding will not stop approval), then in my view the remaining doubt on efficacy will not be hard to overcome by the FDA. When manufacturing and the MOA were in doubt, they could not rely on any analysis presented by Mesoblast on efficacy or even the ODAC vote, and so another trial was recommended.
However, if the FDA can rely on the data presented... then the weight of benefit far outweighs the risk, and the weight of the 9-1 ODAC vote will come into play, as will the impeccable safety profile of Ryoncil and the fact that no other FDA approved products are available for this high mortality disease for children under 12 (up to 90% mortality for severe SR-aGVHD with high inflammation).
We may seem compromise in that it is only approved for sufferers with a high inflammation biomarker, but would be most of the patients and in reality the patient population the most need of this treatment.
Turning away from Ryoncil, which I have high hopes for, the CHF program is coming to a very important junction ... and it will come very soon IMO.
The below slide is a very important one and is worth bringing up and reminding ourselves exactly what Mesoblast have in hand.
While not using the 3 point MACE primary endpoint the FDA has agreed is an approvable endpoint for assessing our Revascor treatment, last week Jardiance just got a label extension showing a relatively risk reduction in heart failure hospitilisation or death of 21% or 3.3 absolute risk reduction.
As a reminder Revascor achieved
19.4% absolute risk reduction in 3 point MACE, which is a much harder endpoint to achieve than what Eli Lily did above, and with a p value of 0.003 and HR of 0.457 (lower is better).
We see most FDA approvals these days for label extensions, which is the norm as it is a much more efficient process (1 vs 2 trials) and the FDA is usually more lenient given prior approval has been given for a certain treatment.
The journey to get FDA approval is a very long and expensive one. Most fail and it is only on rare occasions that new drugs or biologics come to market needed two phase 3 trials. Our CLBP product is one of those, which is on the most expedited route to FDA approval and is highly likely to succeed.
On this occasion the FDA for CHF they are well within their right to ask Mesoblast to run another phase 3 trial given the miss on the primary endpoint, but they are also well within their powers to use their "expert judgement" to approve the product with a single trial.
I predicted that Mesoblast could have already had the meeting with the FDA, if it took the usual 60 days from when they announced they had updated their analysis, until a Type B meeting could be held. But it appears they have waited a while longer to schedule this meeting, and it has got me thinking if Mesoblast waited for Robert Califf to be officially elected before having this upcoming FDA meeting to discuss the pathway to approval?
Mesoblast is known to Robert, through Joanne Kurtzberg who was the lead investigator for our Ryoncil product that is before the FDA as we speak. He is also a cardiologist and a supporter of expedited approval pathways. It would make a lot of sense if Mesoblast waited for his election to be made official before taking this very important meeting... which really could happen any day.
Looking forward to what the FDA have to say, provide pathway to approve based on a single trial or potentially wait 3-5 years for another trial. Either way a partner is not too far away IMO.
Goodluck all
(20min delay)