I found something of interest- Longs- enjoy
Forte said that the majority of regulatory discussions revolve around topics related to manufacturing and specifically practices related to chemistry, manufacturing, and controls (CMC). Drug developers and manufacturers should not view regulators as gate keepers but instead think of them as partners who can help them achieve their safety and quality goals. “Go early to regulations,” he said. “Go frequently, and go well prepared, because if you do that, you will [be better positioned to] take advantage of their advice.”
At the ISCT’s May 2024 meeting in Vancouver, Canada, Forte said that regulators around the world gathered and shared their experiences about CGT development and manufacturing. As such technologies have advanced and more therapies reach various stages of clinical development, regulators are becoming more comfortable assessing them. They have adjusted and calibrated their opinions on topics such as risk aversion as more data becomes available.
Forte cited Mesoblast’s recent work on Remestemcel-L for graft-vs-host disease as a recent success in the field that solved CMC manufacturing elements. Kiji will target the same indication, but with further optimization.
“It’s always important to learn from others and see what we bring on top of that,” Forte said. “[Mesoblast has] done fantastic work on delivering value with MSCs. I think the field is ready to go to the next generation, which is what we propose by engineering the cells. We can do that. We have the technology.”
2023
In GVHD, Schuster discussed Mesoblast’s use of a potency assay as a CQA to measure the immunomodulatory fitness levels of MSC(M)
lots based on inhibition of interleukin-2RA expression in co-cultures with activated lymphocytes [5]. In the January 2023 BLA re-submission [5], Mesoblast provided new prospective analyses to demonstrate that the potency assay is relevant to the primary mechanism of action of remestemcel-L in GVHD and correlated to survival outcomes. Furthermore, the company reported that additional data and
analyses demonstrated low inter-assay variability. Historical manufacturing changes that augmented the immunomodulatory fitness of the product were captured by the potency assay and correlated to improved survival outcomes. As such, Mesoblast set new specifications for release of the commercial product based on the potency assay readouts and clinical data. Notably, the August 2023
complete response letter from the FDA cited no issues with the updated data on this potency assay [6]Below is the link to reference #6[6] Mesoblast Limited. Mesoblast receives complete response from U.S. Food and Drug Administration for biologics license application for steroid-refractory acute
graft versus host disease in children. https://investorsmedia.mesoblast.com/ static-files/422cd6da-a0b9-49cf-a177-7fd106f111f2; 2023 [accessed 9.8.23]
My excerpt form the link - a Mesoblast market announcement.
Prior to the resubmission, FDA guided Mesoblast to resolve outstanding chemistry, manufacturing and controls (CMC) issues before initiating any additional clinical trial. FDA completed the Pre-License
Inspection (PLI) of the manufacturing facility, did not issue any Form 483, and found no objectionable conditions. In addition, FDA acknowledged in the resubmission review that changes implemented appear
to improve assay performance relative to the original version of the assay used in the pediatric Phase 3 trial.
There is a difference in wording here- market announcement - appears to improve assay performance versus the CRL had no issues with the updated data on this potency assay.
Am I just dumb and missed this? Or does it mean that we have two pieces of information from the CRL- Phil Krause - efficacy no longer in question- Michael Schuster(?) no issues with the updated data on the potency assay? See the difference? appears to improve vs no issues with new data??
Add those to @Wilba32 post this morning with the back slapping for Mesoblast solving regulator CMC issues which appear to have been derived after a May 2024 International Cell meeting in Vancouver.
What information is out in the industry that is not market sensitive- perhaps because we await final regulator approval on said CMC items they don't need to update.
But something damn important has happened which appears favourable to Mesoblast.
I would much rather prefer the quotes from Industry Insiders to Anonymous Posters.
"Forte cited Mesoblast’s recent work on Remestemcel-L for graft-vs-host disease as a recent success in the field that solved CMC manufacturing elements."
A good day to all
Not investment advice- this is not a fait accompli
But I do rather like it when something pops up and potentially swings the pendulum our way
Reg
(20min delay)