To understand where I am coming from, let us focus on the most recent change to the trial.
The way I see it the trial was split into two, with the obvious change from one 1165 patient trial to two 600 patient trials (600 patient confirmatory trial is currently still required).
There are obviously cost and flexibility benefits in doing this, and it could have only been possible by changing the primary end-point. A change that I believe actually makes the trial easier to succeed.
The primary end-point was changed to take into account recurrent MACE events from the same patient. Whereas the previous trials were to test the time to first MACE event, so hence you needed a lot of patients.
The reduced population size was agreed as the primary endpoint because it is now measured on the number of MACE events, rather than the number of people in the trial.
IMO this is beneficial to the phase 2 trial showed that over 3 years, treated patients were protected from recurrent MACE events- whereas non treated would consistently have reoccurring MACE events.
So for example if MSC 150-IV really worked and the treated patient was monitored for 1 year and had only one MACE event for example at 3 months.
And the non treated had one every 3 months (4 in a year).
Under the old trial design, both would have had been registered at 3 months as having a MACE event and the trial would end for them both- and the trial would record that there was no difference between treated and mom treated.
However under the new design, the trial continues for both and registers 1 for treated and 4 events for non treated.
Outcome of trial is completely different using the same patient.
The other obvious benefit of this is that it costs a lot less to run this trial. If it fails, well you only incurred half the cost (and time). That was a massive win to get the FDA over the line on that one.
And the benefit of flexibility cannot be disregarded. If the 600 patient trial is successful, they can then go to the FDA and negotiate what the next steps are.
Do they really need to repeat the trial? Or could it be substituted with other data such as the currently running phase 2b trial funded by the NIH which will read out end of 2017? Maybe the Boston pediatric study as well?
This is of course what MSB means by coming back to the market with an updated plan for the CHF program.
A few important things have changed since the trial was changed back in Jan16, namely:
1. NIH 2b trial
2. Harvard's Boston children's hospital trial
3. 21st century cures act
MSB will likely go to the FDA after the NIH 2b trial data is released, and we are sure to get a lot more clarity on the CHF program after that happens.
(20min delay)