You are right.
On the for side we have:
- No safety concerns demonstrated
- ODAC vote 9 to 1 for approval from industry leaders
- Efficacy demonstrated in the sister product TEMCEL in Japan through a phase 4 trial of over 300 patients( Adults and children )
- New efficacy data demonstrated in over 240 children given compassionate use
- Efficacy demonstrated through GVHD001 trial which achieved the primary end points
7. New contemperaneous control arm data introduced by means of a peer paper. ( Same hospital, same time as the GVHD001 trial was occuring, same patients matched )
8. New potency assay that links the assay to survival ( data to counter FDA's observation no link betwen assay TNFR1 levels and survival )
9. TEMCEL and MAGIC database indicates favourable results are expected in the phase 4 expansion in to adults ( when it eventually gets under way )
10. NEW MAGIC predictive biomarker results indicates superiority of Remestemcel as a treatment to patients with gut inflammation. Mortality reductions between 50% and up to 80%.
On the against side we have:
1. FDA questioning the assay regardless of the benefit, and saying there is no link between the TNFR1 and survival
2. FDA questioning the control arm used and saying not enough data has been provided to use the control as a control
3. FDA ignoring ODAC's advice to approve the treatment
4. FDA stating that potency assays need to be validated prior to commencing and ARDS trial
5. FDA questioning the measure of efficacy as a direct result of them questioning the control arm
6.FDA recommending another trial instead of mesoblast fixing issues 1 - to 5 using current data.
We know that Mesoblast have said they now know it is essential to link potency assays to survival outcomes
We know they have altered somehoiw the data or the assay to show this
We also know they will supply the Magic biomarker analysis which provides an even more convincing layer of proof about the control arm, one that was not available for the original BLA, and one that will hold quite a lot of sway in the context of things
We also know they will remind the FDA of ODAC's 9 to 1 vote for approval, in a disease with unmet need, no treatments and a high mortality rate.
The question is, have MSB answered enough of 1 to 5 with the available data they have, in the context of high mortality, unmet need, no approved treatments and 9 to 1 vote of approval from industry?
Obviously if what Mesoblast have released is correct. The assay does link TNFR1 to survival, and there is a reason as to why it did not previously, they backup the control arm data with 3rd party unbias analysis so further efficacy can bee seen..... then in the eyes of the FDA there would be no need for another trial, since it was only a recommendation of a way to address the other items in the CRL, and not a standalone requirement of any sort.
I hope they get through second time around, and industry agreed with me.... 9 to 1.
It is the leading edge of medical science.
(20min delay)