Good post. The FDA were blindsided by the MAGIC study since MSB...

Good post.

The FDA were blindsided by the MAGIC study since MSB did not include it in the BLA, but instead included it in their presentation for theODAC meeting - so the FDA never had any time to go over the data beforehand. It was meant to represent the worst of the worst of sufferers and only included a small subset of matched patients with bloodwork done at the time, so not as an entire control cohort.

One of the issues noted was the calculation used for the historical control. Another was the failed GvHD trial performed earlier, from which MSB conducted post-hoc analysis to identify certain groups that may benefit from the treatment, namely the worst sufferers. MSB regarded this trial as an RCT and while it was an RCT, the primary endpoint was not met. An additional issue was concerning the MOA and how the MOA did not associate with improved outcomes except only when the data was pooled. Unpooled data showed non-significant outcomes.

MSB then started treating pediatric patients via a EAP to confirm the post-hoc results from the earlier RCT. Confirmation of these results made it unethical to conduct a RCT in pediatric patients according to MSB and KOL's. The FDA however recommended that MSB conduct at least one RCT due to the above.

There was however a workaround that may have allowed MSB to avoid another RCT since all MSB needed to do was prove is Rem-L is "safe, pure and potent". Potency refers to efficacy from which MSB relied on the ODAC vote of 9-1. However, all other efficacy indications are also included in this measure, including the initial failed RCT. So since MSB did not meet the threshold of "at least one well controlled study" in the eyes of the FDA. MSB now find themselves having to conduct an RCT that must be adequately controlled.

Has SI learnt his lesson? Probably not since he already shot down the possibility of including a placebo group.It seems as if he is already thinking about another "workaround" when in reality he may just have to bite the bullet and include a placebo group.

The biggest lesson from today IMO is to bring on board some good people with a biomedical background. MSB has zero, PAR has zero, a lot ofbiopharma companies on the ASX have none. The reason is because biomedical scientists are trained specifically in all processes from bench work to clinical trials and trained to understand the expectations of the FDA. And most importantly, most of the FDA reviewers have a biomedical or related background.