Ann: Mesoblast and FDA Align on Key Items for Revascor BLA, page-130

Bringing up the past is not good for the blood pressure however this meeting would be the first time the new administration has taken a deep look into GVHD and the treatments given. They would be looking at the above study and many others. There conclusion to this trial would I think be along the lines of "response is not a indication of OS" They would also pick up on the statement .

"the response on day 28 was not found to be associated with ruxolitinib doses in the REACH1 study.²¹ "
REACH1 failed its soft primary endpoint of response @ 28 days
Yes that's right FAILED, "The targeted ORR at day 28 was 60%." . They got 54.9 but look how it dropped in Grade 3 and 4, just 42%


I don't know how they got 60% as the target however I found it interesting to see that they felt if they got 37 responders the trial would be considered positive OK they got 39 , just 3 less and this trial would have not only failed to show meaningful benefit , it would be considered to have a negative outcome. As you can see above 60% as a pre determined goal is a fairly futile number as the distribution of class 2 too 3 and 4 would have significant effect on response. Regardless of how they got 60% as a target the trial was very badly designed. Perhaps even unfit for purposes.




So how will the FDA view this?
Would they consider adults with grade 3 and 4 GVHD to have no effective alternative despite Rux approval. This will have significant implications for our trial design and development program. Due to the poor association of ORR @ day 28 that Rux has shown FDA should consider AA for above as we already have substantial data. Confirmation of benefit would be from real world evidence of OS and quality of life measures post approval. FDA might even try out there 2 month BLA process after all it is only a lable extension.

GLTA