Ann: FDA Notifies Clinical Data Sufficient for Refiling aGVHD BLA, page-680

FDA says no to the BLA data and issues a CRL
Phil Krause tells us the specifics of the CRL- the product used in 001 was effective- provide more data re Ryoncil characterization and standardization or start again with a new trial.
FDA later changes it's position and allows the BLA process to restart.
Company says we are back on track.

August 4 2023
BLA received- Mesoblast says we will run a trial in adults to obtain the data the FDA requires.

August 30 2023
Dr. Philip Krause: Sure. I will make a quick point here and that is the CRL had, although, of course, the disappointment of being a CRL, but had two positive indicators in it as well or two significant positive indicators. One of course was the favorable results of the inspection, but the other important thing to take note of is that, the CRL did not question the efficiency of the product as was demonstrated in GVHD001, as had been the case in the previous CRL. But the CRL did continue to question and raise questions about the potency assay. And specifically, the characterization and standardization of product that went into GVHD001, and then the ability then to make future product that was similar to that, which went into GVHD001.

And so, this leaves open the real possibility that by using exactly the same assays that were used to characterize the product going into GVHD001, for a new commercial product that it would be possible to show that the new commercial product is similar enough to that, which was shown to be effective in GVHD001. Now, the CRL then went on to say that, if that can't be accomplished, in other words, this demonstration, then the only way forward would then be another clinical trial in either adults or pediatrics, which would then allow this connection between potency assay and clinical outcomes to be made, and thus allow future product to be related to product that was shown to be effective in a clinical.

John Hester: Maybe just one follow-up Mr. Silviu, if I may. What are the fundamental changes between the product that was used in the 001 trial and the product you were now attempting to have registered?

Dr. Silviu Itescu: I can address that. There were no changes. The same exact manufacturing process and the same product went into the Phase 3 trial as it's currently in inventory and intended for release. And that's really what the inspection of the process and the plant and ultimately concluded. So, there are no changes to the product. What we need to ensure is that, we have a potency assay in place that was used precisely in that Phase 3 that continues to demonstrate the same attributes of the existing inventory. Phil, would you add anything to that?

Dr. Philip Krause: I would not. I think that's exactly right. The manufacturing process has not changed.

Operator: Thank you. That brings us to the end of today's call. I will now hand back for closing remarks.

Dr. Silviu Itescu: Great. Thank you everybody for joining us today. We hope that we have been clear in providing details around our interactions with the FDA our upcoming Type A meeting,


March 26 2024
Melbourne, Australia; March 26 and New York, USA; March 25, 2024: Mesoblast Limited
(ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases,
today announced that U.S. FDA has informed the company that following additional consideration the
available clinical data from its Phase 3 study MSB-GVHD001 appears sufficient to support submission of
the proposed Biologics License Application (BLA) for remestemcel-L for treatment of pediatric patients
with steroid-refractory acute graft versus host disease (SR-aGVHD).
“We thank the agency for their collaborative approach. The responses and guidance from FDA are clear
and provide us with a high level of confidence to refile our BLA for remestemcel-L in children with SRaGVHD,” said Mesoblast CEO Dr. Silviu Itescu.

April 29 2024

• Mesoblast will now focus on its original strategy to first gain pediatric approval for RYONCIL, followed by label extension in the larger adult population.
  
  The meeting after the CRL was a Type A -
  • Meetings to discuss clinical holds in which a response to hold issues has been submitted,
  but the FDA and the sponsor or applicant agree that the development is stalled and a new
  path forward should be discussed
  
  The meeting where we got the nod to proceed was a Type C
  • A Type C meeting is any meeting other than a Type A or Type B meeting between CBER or
  CDER and a sponsor or applicant regarding the development and review of a product.
  
  
  The new data presented to the FDA was sufficient to restart the BLA process- we outsiders are only privy to Phil Krause's statements- the only way forward has reverted to the original plan.
  
  If only I was a betting man
  
  Reg