Those who listened to the ODAC committee morning session would...

Those who listened to the ODAC committee morning session would no doubt recall the negativity of the FDA rep. I realise he was just doing his job, and in the long run, the fact that the FDA played a hard game could be a considerable advantage imo.

Amongst the FDA concerns were criticisms of the 'critical quality attributes' MSB proposed to use to measure the consistency, potency and effectiveness of batches of remestemcel-l.

From the briefing notes, the “FDA’s position is that the product attributes the Applicant has identified as related to potency and activity of the product, however, do not have a demonstrated relationship to the clinical performance of drug product lots, ....” And on it went.

My science qualifications are a little rusty, but it’s my understanding that Mesoblast believe the quality and potency of its MSC cell product lots can be gauged through monitoring the frequency of a number of cell surface markers, and particularly by the cells ability to inhibit production of the inflamatory cytokines, TNF-alpha and IL-2R alpha. The FDA weren’t convinced.

I suspect backroom discussions between the FDA and Mesoblast have been ongoing since August 13th. If the mechanism for monitoring quality and potency of MSC’s really is a stumbling block, it needs to be resolved.

Now by coincidence, a large study of Covid-19 patients in the Mount Sinai health system was published yesterday.

The study followed the clinical information, laboratory test results and patient outcomes, of 1484 individuals hospitalised with Covid-19 earlier this year. Long story short, the researchers concluded that high serum levels of IL-6 (P<0.0001) and TNF-alpha (P=0.0140) remained independent and significant predictors of disease severity and death, regardless of demographics and comorbidities.

Thinking out aloud again, given that remestemcel-l is proposed for use against both aGVHD and Covid-19,  MSB already has TNF-alpha covered. I wonder what the FDA think about IL-6?

Nonetheless, my view is that, at least in paediatric conditions, if a treatment is safe and it works, that's enough. The Advisory Committee clearly agreed. 9-1.

Disclosure. I’m biased.

https://www.nature.com/articles/s41591-020-1051-9#Tab1

Herro