@bedger@chucke For some time now Mesoblast has been hinting that something CMC related in the past is responsible for the last major outstanding issue behind their receiving a second CRL. The irony is the FDA might well have been over concerned about problems encountered with higher batchvariability by Osiris in their two older clinical trials using Prochymal under different manufacturing conditions. Mesoblast achieved its primary endpoint in a Phase 3 trial GVHD001 which was powered to show a response above 65% to obtain statistical significance against historical controls of 45% for 28 day response which still is the widely used primary surrogate endpoint for clinical trials in aGVHD.. As @chucke correctly reminds us, issues of batch variability have not been highlighted nor efficacy questioned with regards to the EAP. The fact that the recent FDA manufacturinginspection (and the internal and external mock audits) of the Lonza facilty in Singapore were successful, strongly suggests to me that this CMC issue has been resolved because it would have involved production runs using the new assays. This is obviously not enough for the FDA..who wanted potency assays developed which identify not just T Cell suppression but could ensure consistent cell characterisation via a potency assay that would speak to the health and viability of the MSCs. If I am right the Company will be aware that they must provide a dataset using their new assay that can identify batch variability…which can then be backtested for accuracy against the previous defective and non defective cells used by Osiris. Put simply the FDA would appear to have worked out that our cells work they just want to know why Osiris had higher levels of batch variability. If Mesoblast are unable to provide this information then they recommend an additional trial in adult or paediatric. Perhaps it should be noted that Osiris did not have a contract manufacturing relationship with Lonza at the time and their CMC might have been unable to detect subtle changes, not necessarily to the initial feedstock but to how the manufacturing process itself which is extremely complicated, might affect outcomes. I read general research on MSC harvesting in the past regarding factors such as shear stress, confluence rates , different cryopreservation techniques, washing off growth media , concentration and packaging all of which can affect or damage the TLR receptors on MSCS reducing potency entirely independent of the purity of the cells themselves.
As i write this the latest quarterly has popped up.
Mesoblast Chief Executive Silviu Itescu said: “It has been a very busy quarter in which we have madesubstantial operational progress across our three lead Phase 3 assets. We have generated significantnew 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 FDAthis quarter.”
I reckon they have nailed the potency assays. I suggest that this will become obvious if the FDA agree to use them in the next adult trial being undertaken. If a consensus is reached that would open up a clear path to accelerated approval for paediatric . Lets hope. Great to see a CRO has been engaged for CLBP. My timeline is nine months for recruitment.
Please do not rely on the facts or opinions expressed in the above post when making an investment decision.
MSB Price at posting:
27.0¢ Sentiment: Buy Disclosure: Held
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