Ann: Trading halt, page-612

Left-e1 hour ago

For newcomers to the board, Mesoblast (symbol MESO in the US and MSB in Australia) was placed on a trading hold a little over 24 hours ago pending a “corporate update” expected no later than Friday in Australia (Thursday evening in NY). There has been much speculation on this message board and on the Australian message board “Hot Copper” (HC) as to the cause for the halt... everything from a capital raise to major personnel changes (SI = Silviu Itescu, CEO) to a buyout to a communication from the FDA (regarding the Company's type A meeting on remestemcel-L for GvHD) to a communication from the DSMB (regarding the Company's phase 3 trial of remestemcel-L for Covid-19 ARDS for which the Company is partnered with the NIH to conduct the trial and with Novartis to eventually market the product). I personally suspect the latter. Realizing such DSMB communications can be either positive or negative, I thought I would review some rough numbers. Even if the halt turns out to be for other reasons, the DSMB report is imminent in any event.
The trial is scheduled to enroll 300 patients with critical C-19 ARDS within 72 hours of placement on a ventilator and the primary endpoint is survival at 30 days. We are awaiting the 3rd interim readout of the trial after the first 180 patients have reached the 30-day mark after enrollment. That would be 90 patients treated with remestemcel-L plus Standard of Care and 90 patients treated with placebo plus SoC.
Here's a SCENARIO: Based on findings from the 12-patient EAP conducted in April we might expect 83% of remestemcel-L patients to survive. That would be 75 patients. What about the placebo group? We know SoC has been improving, but for patients ending up on a ventilator management has told us mortality rates are still in the 60% range. Out of 90 placebo patients that would be only 36 survivors. In other words, the gross prediction is 54 deaths in the placebo group vs 15 in the rem-L group. A rem-L mortality reduction of 72%, even better than we just saw with rex-L (a different product) with the CHF trial. 39 additional deaths prevented in a group of 90 is something that would probably sway the DSMB – given that another 120 patients are scheduled to be enrolled to complete the trial. 60 placebo and 60 rem-L. At these rates it means 26 SoC lives would potentially be in jeopardy out of 60 enrolled. That should be enough to sway the committee. Like the referee in a boxing match their primary job is to step in and call the bout if one side placebo vs rem-L is literally getting pummeled to death. If there is no doubt as to outcome. Big differences in mortality between the two groups are thus necessary to call it early for rem-L. If there's a moderate difference, the study will continue (without a trading halt). If there's no difference, or somehow rem-L patients do worse, the trial could get called for futility, like we just saw with Pluristem. And that would also result in a TH. Numbers may vary from this SCENARIO given treatment changes for C-19 since April. So there's no way to predict for sure. GLTA

Left-e27 minutes ago

I'll add that the trial has been going on since May so a number of the patients enrolled back then will have reached the 3-month and even 6-month stage. A number of secondary endpoints are being monitored and big differences there would probably also sway the committee. Of great interest is whether rem-L can reduce the incidence of pulmonary fibrosis which contributes to delayed recoveries, re-admissions, and so-called "long hauler" syndrome. Note that even if the DSMB calls the study early in favor of rem-L, the study will continue for at least a year if not longer. It's just that new placebo patients will no longer be enrolled. The company will probably discuss with the FDA whether any surviving placebo patients already enrolled will be allowed to "cross over" and receive treatment with rem-L.

fred12 minutes ago

Left-e
As usual, well-articulated prediction. Your postulated 72% efficacy with MSCs results from an 87% replication of the NYU efficacy data in only 12 patients and 60% mortality in standard of care. Two prior peeks by the DSMB must have seen positive data. However, The possibility of less than such an ideal numerical result would occur from: a lower efficacy; a more modest mortality- 40%-50% mortality in SOC; or both. That should still gives a result less than 72% in your scenario which is obviously spectacular BUT above the 20% efficacy some have entertained would be required by the FDA.
My guess is that there will be efficacy above 20% but that the DSMB requires this study go to completion.
We shall see shortly...