CEO Itescu needs to go, page-787

@irenekwshiu,

I already replied to the post by @Phaedrus a while back. It's not clear how he proposes to do a "prospective, controlled study" that's "Not randomized and Not placebo-controlled". I think RWE is what got us into the current situation, and I don't think it will get us out. He's over-reading the PR, imho. FDA wants RCT data... and that's why SI is moving to adults to get it.

Yes, that "pesky legacy concern" is what this is all about. Assuming safety, the FDA null hypothesis is that the medication is ineffective and will give the same results as seen in controls.. Efficacy must be proven in comparison to the control group receiving a placebo or SoC. But finding an appropriate control group is not so easy with an illness like GvHD. It's a complex complication of already very sick patients... multiple organs can be involved, and multiple other medications in various combinations may be used to treat SR cases. I posted a list earlier. Non-medication treatments such as ECP may be used. If patients are chosen from a database, do they represent current SoC? Part of the FDA concern is that ORR was under-estimated and mortality over-estimated in the historical controls (perhaps unintentionally), thus making rem-L shine in comparison. The FDA could be wrong too... as @otherperspective points out. Maybe they're holding Mesoblast to a control standard that's too tough. I don't know. The scientific way to find out is to run well-constructed prospective phase 3 RCT's, as with most other medications. The company has done that for other indications... so it's not clear why SI insists on advancing this one first... BECAUSE even IF we grant the null hypothesis proposed by the company, the data are statistically weak for mortality reduction. imho