Ann: Mesoblast Phase 3 Chronic Low Back Pain Results, page-254

Opioids reduce CLBP pain by 10-15 points (with extreme side-effects), our cells achieved 30+ point reduction over 24 months with no side-effects, and in fact lead to a reduction in opioid use.

That is unprecedented when it comes to treating CLBP.

Function component of the composite endpoint was not met across the entire study, and would have just missed out by a little if the <5 year population subset was used using ODI (24 month was at p=0.059), or a composite using ODI at p=0.06. It would have been met if they used another measure of function i.e. EQ-5D Index. It's something patients value when looking at a CLBP treatment, which is why the FDA want it measured. If another trial was conducted, I suspect it would be a secondary endpoint.

but at the end of the day, this treatment works in reducing CLBP from Degenerative disc disease .. with a marginal miss on functional 24 month end points using ODI, but would have met using EQ-5D Index. Does EMA/FDA or potential partners ignore a 35+ point durable reduction in pain with no side effects + reduces opioid use because of a question mark on function?

That's the question the market is grappling with... hence the indecision... but there is no doubt that the treatment reduces pain for CLBP sufferers by a magnitude not ever achieved before.

Next step is to meet with the EMA to design the next trial in Europe, and whilst I don't know what it will look like.. I suspect it'll be a 12 month reduction in pain as a primary endpoint, with a key secondary endpoint in improvement in function. Very high likelihood of this trial going ahead with Grun.

Also to meet with the FDA to discuss potential for accelerated approval or a confirmatory study based reduction in pain and opioid use reduction was not really on my radar... but that is another pathway to approval and partnership. FDA guidance on Opioid Use Disorder