@timmyjuly Apart from being repeated at each quarterly update by...

@timmyjuly

Apart from being repeated at each quarterly update by Silviu, you need not look look any further than the announcement on 29 March 2018 where the CLBP phase 3 trial completed enrollment.

Fourth Paragraph:

"The phase 3 trial's primary endpoint is in line with written guidance from the United States Food and Drug Administration (FDA) in support of product registration, and specifies:

- use of a composite measurement showing significant clinical improvement in pain and function at both 12 and 24 months;

- pre-specified threshold for determining significant improvement in paid (50% decrease in Visual Analog Score) and function (15-point improvement in Oswestry Disability Index)

- patients who undergo additional interventions at the treated level are considered treatment failures."

There is no reason to increase the patient population of a trial unless the sponsor (MSB) is unable to demonstrate a statistically significant outcome against the primary endpoints. In which case another phase 3 trial can be initiated (usually with a higher patient population) to meet the primary endpoints agreed with the FDA, or new primary endpoints can be re-negotiated.

It is important to make clear that Mesoblast need only demonstrate a statistical significant result that demonstrates the above, with the initial 360 patient trial now a 404 patient trial making it larger than initially agreed with the FDA.

Below are a couple of links that will help you understand how the FDA clinical trial process works, both easy to read.

The FDA website suggests that a typical phase 3 trial will have between 300-3000 patients.
FDA website

Here is another good page from the FDA that shows that the FDA and sponsor (MSB) would have discussed and agreed the size of the pivotal trial prior to commencing .
Detailed Phases of FDA trial

Extract:
"At the end of Phase 2, the FDA and sponsors try to come to an agreement on how large-scale studies in Phase 3 should be done. How often the FDA meets with a sponsor varies, but this is one of two most common meeting points prior to submission of a new drug application. The other most common time is pre-NDA--right before a new drug application is submitted. "


The CS Analyst has worded their downgrade very cleverly to make it seem like the reader should be concerned about the need for additional patient data for the back pain and LVAD trial, what they don't clearly articulate (but imply) is that you should only have this concern if the trials fail to meet their primary endpoints.


I would encourage you to re-read what the CS has actually written to justify the downgrade, paying careful attention to the wording used and see if what I say is indeed correct.