Ann: FDA Advisory Committee Sets Review Date for Remestemcel-L, page-741

Thanks for that reply @Zenox

You are absolutely correct with your second point and it's on my list of reasons why the FDA may issue a CRL next week. There is A LOT at stake with this trial, as you state there are over 1000 cellular therapies in clinical trials in the US alone... and there are no FDA MSCs in the US.

If MSB become the first approved MSC in the US, then every single sponsor using MSCs or any other cellular product will use this approval process as a benchmark.

The FDA will not want to lower that benchmark by conceding too much ground, but on the other hand they cannot make it too high so that it becomes insurmountable and not feasible for sponsors to meet.

My thought on this is that what the FDA wants may not be possible or ethical to determine.

Every time MSB puts up data and analyses to support their understanding of how the CQA's relate to efficacy or product quality, the FDA are unable to accept their analysis because it is not discernable in the trial data (in vivo). In order for MSB to unequivocally satisfy the FDA's concerns, they would need to dose patients with remestemcel-l that they consider an inferior quality vs a high quality product... and if the FDA require a sponsor to run a new clinical trial to address something like this, firstly would pediatric patients or their families agree to enroll their child into such a trial, and secondly this would set the bar extremely high.

In my opinion, it may deter many from even seeking to advance their therapies, because the practicalities and hurdles could be seen to be insurmountable to get FDA approval.

If however the FDA concede that this is a new line of medicine and as more therapies get approved, more data is generated across the industry and more companies are contributing to the universal knowledge bank ... then appropriate time to raise the bar may be in line with the progress being made in understanding MSCs over time. Well that is what I hope anyway.

On an unrelated thought, I wanted to highlight the impact of an approved FDA product vs a product that is only available through an EAP. For those who listened to the PM session, and in particular the public speakers... it gave a powerful perspective to what a family goes through when their child is suffering from SR-aGVHD. Specifically the thought process they go through when they are presented with an opportunity to enter into a trial with an experimental MSC treatment.

Firstly, the word experimental is a huge barrier... compounded with the fact that it is a stem cell and all the negative media and history of stem cells is enough to deter many from accepting this treatment in fear it may cause unknown side-effects.

If Ryoncil is approved by the FDA, that not only raises the awareness of this product.. most importantly, it gives families the assurance that this product is safe and effective. It's not an experimental treatment... it works and it is safe for your child. That change in mindset is powerful and one that could mean life or death of someone's son or daughter.