Catching up on some previous questions sent my way....
1) I would disagree that "no company official acknowledged a problem with the potency assay until Dr. Eric Rose...." The company, ie SI, provided this guidance in it October 2020 announcement of CRL 1: "The FDA also identified a need for further scientific rationale to demonstrate the relationship of potency measurements to the product’s biologic activity. Assays measuring the potency of remestemcel-L will continue to be refined to provide further scientific rationale for its use in severe inflammatory diseases with high mortality risk, such as SR-aGVHD and COVID-19 ARDS." Yes, I agree panelists didn't get to see those data... but they weren't asked to vote on that issue... It's why I've said for some time - if there's any concern with the FDA it revolves around that issue... the company did a rolling submission of information in its BLA... IF the FDA had a deep-seated problem with CMC issues, which they did express during the ODAC hearing, why did they empanel a committee of experts to vote on efficacy in the first place?? The potency assay issue should have been picked up in the rolling submission or addressed before going to the trouble of an ODAC hearing. In essence, FDA said, "We're not sure the product can be made in a uniformly potent fashion... but please give us a vote on efficacy of a product we can't be sure is made with uniform potency. That's nonsensical. Most likely answer is bureaucratic inefficiency (as opposed to corruption).
2) and 3), Insufficient evidence of ?? Regarding data, shareholders never get to see "all the data", and they generally don't get to see full content of a CRL. There's confidential and proprietary info in there. Regarding chi-square, I've analyzed the mortality data above... chi-square is not the only statistical tool available but it's good for + vs - data, such as mortality. Very straight-forward. Pt died at 100 days or survived. Patient received rem-L or didn't. That generates a 2 x 2 table that's easy to analyze. FDA no doubt uses additional tools, but the data need to get by chi-square first.
Bottom line, as investors we have to trust that management is able to size up a product candidate and the obstacles to approval and navigate the regulatory maze. I no longer have confidence SI is able to do that... And I now question whether GvHD in children should ever have been pursued as a lead indication with a product like rem-L. Of the multitude of indications out there, why choose that one? The initial efficacy signal in study 280 was not close to being statistically significant. It involved a small number of children cherry-picked out of a larger trial that failed... so we're off to a bad start. Only 13 controls and those were the only prospective, randomized, blinded controls submitted to FDA in the two BLA's. So when the experts say, "can't do an RCT in children for ethical reasons" and when the FDA says in CRL 1, "You don't have enough data", I think you're obliged to pursue adults or some other indication first where RCT's can be done. Prove the product is effective, don't coddle it with uncontrolled studies and EAP's and certainly don't dispute the FDA. ... put your own oxygen mask on first with successful RCTs and an approval elsewhere, then go help the children with GvHD. Because there's a very fine line between "helping the children" and using the children as a regulatory foil. imo, Left-e
MSB Price at posting:
36.0¢ Sentiment: None Disclosure: Held
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