Ann: FDA Notifies Clinical Data Sufficient for Refiling aGVHD BLA, page-793

Hi @Hawk70,

re your request to be shown " ... where the available clinical data from its Phase 3 study MSB-GVHD001 ... goes in any way toward confirming the MSB-GVHD001 Potency Assay is consistent with the standard required for FDA approval.", there's a short-answer & some rather long ones.

Let's go with the short one for now.

You're referencing the 21 September 2023 ASX update from MSB on key outcomes of the Type A meeting with the FDA on RYONCIL - link here. You focus on these words in the update:

" ...FDA clarified that the key remaining issue for pediatric approval is providing further evidence that the potency assay will assure the consistent efficacy of commercial product. "

But these words don't refer (IMO) to the 'MSB-GVHD001 Potency Assay' i.e. either the release potency assay or any in-line manufacturing assay on potency CQAs as spec'd at the time of the trial.

As I read it, the ASX update is here referring to a revised potency assay - i.e. one 'improved' from any assay in place during the 2016-2018 trial. This new-ish assay is at least one of the assays which you'll recall the FDA had just inspected and signed off on in May 2023, as part of the validated Lonza Biologics Tuas RYONCIL manufacture processes.

Mesoblast is saying here that - notwithstanding the PLI signoff - FDA still wants further & better assurance of 'consistent efficacy of commercial product'.

A longer answer to your question necessitates digging down on the real question i.e. to what 'commercial product' was the ASX update of 21 September 2023 referring?

Since it's not the trial lots themselves as used in the trial (whose potency was demonstrated by the trial), and it's not future manufactured lots for which the PLI verified that Lonza's validated processes/ methods (including assays) are in place, and its not lots used in EAPs or otherwise lost to waste & which have been adequately accounted for to the FDA, so it can really only be some/allother RYONCIL lots manufactured under the unaltered manufacturing processes since 2016-2018, presently in existence & held in cryostorage for potential future release.

This product is 'commercial' because Mesoblast intends to sell it in the US market immediately on FDA approval for marketing & deliver it for immediate use.

There's a much longer version of this answer looking at the question of characterization using the new potency assay data which MSB then set out to generate for RYONCIL i.e. to demonstrate to FDA that the product used during MSB-GVHD001 was standardized as to its identity, strength, quality, purity, and dosage form to give significance to the trial.

Why was that important still in September 2023, you ask.

Well, remember that the FDA rejected the comparability study which Mesoblast had tendered to it prior to ODAC in 2020. They needed a new one on CQAs acceptable to the FDA i.e. to 'demonstrate' that RYONCIL lots were not comparable with PROCHYMAL lots. Simply, it took until late last year for the FDA to pull its finger out of its ass & decide what those CQAs were going to be to allow anything to be 'demonstrated' to it. The long-term survival data was critical in making that case, I expect.

And, of course, we can also speculate logically from where that last para. takes us in terms of characterization of cryostored product, cell viability & post-thaw assays. But we're very close now.

I hope that assists for now.

Cheers,
GLTA(LT)H