Musings for the week ... "US FDA has informed the company that...

Musings for the week ...

"US FDA has informed the company that following additional consideration the available clinical data from the phase 3 study MSB-GVHD001 appears sufficient to support submission of the proposed BLA..."

My opinion only, but on reflection the above communication from the FDA seems to suggest the FDA have had internal discussions since the Type A meeting September 2023 and the most recent correspondance (at or ahead of the March 2024 meeting).

It could do with the draft guidance released in November 2023, and the new OTP structure (previously OTAT) which has been on a hiring spree and has said that they want to move away from static written responses with sponsors, rather they want to engage in verbal dialogue with sponsors to improve collaboration / communication between the agency and sponsors.

Anyway back to the draft guidance (link below, and some extracts) now clearly allows data generated from EAPs (if the EAP data is of sufficient quantity and quality) to be confirmatory data. @ddwn you mentioned you always thought MSB would get approval for pediatric SR-aGVHD, using the adult SR-aGHVD as the confirmatory data .. but wasn't sure which pathway that would take. This could actually be the framework the FDA needed to move their goals posts, this time in favour of Mesoblast i.e. allowing the FDA to lean on data generated outside of the phase 3 trial itself, such as EAP data, to demonstrate and support the MOA, including potency assays data and analysis.

Could the "additional consideration" have been the FDA reassessing the quantity and quality of data generated in the EAP and concluding that it can be used as confirmatory data under this new draft guidance? If so, the hard line stance from the initial review of 'they can only consider data from the phase 3 trial for approval' may now be that the FDA can lean on EAP data, when in the initial review they basically ignored it...

Keeping in mind Mesoblast have always provided and continued to provide EAP data to support their arguments, but it seems the FDA seemed to not put any weight on that data (just look at how they talked to the EAP data at the ODAC...). I think the new guidance provides the framework to allow the FDA to fully approve Ryoncil without additional confirmatory data/trials.

Substantial Evidence from a single study and confirmatory data