The interview given by Silviu to The Australian versus official announcements-
Type A meeting September 21st 2023- Announcement says-
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.
FDA noted that the lack of a suitable potency assay for the RYONCIL product used during the Phase 3 trial MSB-GVHD001 for the pediatric acute GVHD indication has prevented the trial from being considered an adequate study for the purpose of demonstrating substantial evidence of effectiveness required for a marketing approval.
Mesoblast intends to generate in the coming months new potency assay data for RYONCIL showing that the product used during pediatric Phase 3 trial MSB-GVHD001 was standardized as to its identity, strength, quality, purity, and dosage form to give significance to the results of the investigation as described in the Code of Federal Regulations for adequate and well controlled studies (21 CFR 314.126), and that commercial batches made for the pediatric indication will meet the same standard.
Mesoblast Chief Executive Silviu Itescu said: “We had a very productive meeting with the FDA’s review team, allowing us to establish the path forward for potential approval of remestemcel-L in SR-aGVHD. We are gathering the additional potency assay data required to demonstrate the ability of Mesoblast’s
potency assay to show both the product used in the Phase 3 trial in children and the product made for commercial release are standardized.
The company did not make public any feedback from the Type A meeting minutes.
From the Annual Report- Silviu Itescu- 30/10/2023
Further, to support approval for the pediatric indication, we are currently generating additional data using the IL-2R alpha inhibition potency assay which was in place during the pediatric Phase 3 trial to provide the needed link assuring consistency between the RYONCIL product that was used in the pediatric Phase 3 trial and available commercial inventory
15/11/2023 Corporate Presentation
Mesoblast believes that the totality of these clinical studies, together with additional potency assay data currently being generated using the IL-2R alpha inhibition potency assay in place during the pediatric Phase 3 trial, will both support approval for the pediatric indication and provide a link between the
RYONCIL product that was used in the pediatric Phase 3 trial and available commercial inventory.
January 31st 2024 December quarterly- This is the first reference to now having the data requested by the FDA.
Silviu- " We have generated significant new potency and characterization data for our lead product Ryoncil® (remestemcel-L) for children withacute GVHD, as requested by FDA, and will submit these data ahead of our planned meeting with FDA this quarter.”
February 26th 2024- Webcast - Silviu confirms new data has been provided to the FDA.
February 29th 2024 Quarterly Q2 - under the Manufacturing heading.
Costs in the current period include new potency and characterization data for the remestemcel-L product, as requested by FDA, which have been submitted ahead of our upcoming meeting with FDA next month.
March 26th Announcement
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).
So the FDA had the newly generated data for at least one month , to review.
The Australian
- Prof Itescu " We met with them at FDA headquarters in September, we re-presented our data to a group of the leadership........" Mesoblast was asked for additional data, and went back to the FDA in January, expecting to be told what more needed to be done on the study front.
" And instead , what they said was 'no, we've thought this through, and you've convinced us that the clinical data are very strong'" Prof Itescu said.
" You've got enough to get approved for children- go ahead and file.............."
Breaking this all down - the FDA was not satisfied in the first instance that the Phase lll was an adequate study due to issues with the potency assay and
( unknown) other product characterisation issues.
The company provided new data and the FDA - my words- must now consider that the Phase lll was a well controlled study with a suitable potency assay. The other ( unknown) product characterisation issues still needing to be resolved.
D. Class 2 Resubmission - A resubmission that includes any other item not
specified as a Class 1 item, including:
1. Any item that would require a presentation to an advisory committee.
2. A new manufacturing facility(ies) or would warrant a follow-up assessment
and/or inspection of manufacturing facility(ies).
3. Any data other than minor assay validation.
4. Any resubmission with large amounts of data such as data to support
process performance qualification.
Number three fits the determination of a Class 2 resubmission, which is why we get designated a 6 month PDUFA date.
The Australian
Prof Itescu said the company was now well placed to progress its plans with about five or six quarters of cash . He didn't see a need to raise more capital and as the company was looking at potential revenue in the near to medium term it was " well cashed up. "
Consider that the FDA does not need to review any more clinical data- will not hold an Adcom- is good to go for the potency assay - is satisfied with the manufacturing processes, no safety issues, no longer questions efficacy. Had questioned consistency of efficacy in the past.
We are now left with whatever the hell those additional CMC items are - and Final Labelling.
Personal opinion- no cap raise until we get a decision- which is likely to be quicker than most imagine
Reg
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(20min delay)