Cell Therapy News/Articles, page-1559

Thank you again Left-e from Yahoo chat.

Left-e
Some significant differences in the announcements from Mesoblast compared to Athersys for the Covid-19 trials. First, Mesoblast has a partner: “This trial will be conducted as a public-private PARTNERSHIP in a collaboration with the Cardiothoracic Surgical Trials Network (CTSN), which was established by the US National Institutes of Health’s NHLBI”. Athersys: “This trial will be conducted at leading pulmonary critical care centers throughout the United States.” No partner announced, but they are in discussions with BARDA. Second, study size. Mesoblast will evaluate “240 patients with ARDS caused by COVID-19” in a “...multi-center Phase 2/3 trial” Athersys will “enroll approximately 400 subjects... The first cohort will be open-label with a single active treatment arm to evaluate the safety of MultiStem at two dose levels. The second cohort will be a double-blind, randomized, placebo-controlled run-in phase to evaluate efficacy. The design of the third planned cohort will be based on analysis of the results of the second cohort.” So, what does that all mean? First, despite having completed a phase 1 / 2 trial with 36 patients, Athersys hasn't yet convinced the FDA on dosing. And they used a hefty dose, 900 million cells per patient, in the high-dose part of their phase 2. Dosing is squarely a phase 2 issue. Main implication: it will burn time and money before the real efficacy trial can begin. Mesoblast may have to do the same thing, we'll see when the trial parameters are published. But they have already treated over 1100 patients including 60 in a COPD (pulmonary trial). So the fact that only 240 patients are required now means they'll be able to get this done faster and for less money. Athersys is using a “run-in phase” in the efficacy cohort, meaning patients will be enrolled in the trial, observed for a certain period, and then possibly removed from the trial before randomization to treatment vs placebo. Not clear why they are doing that or if Mesoblast will do the same; it does introduce a hurdle for sick patients and another variable that will require scrutiny. Athersys has come under attack for the reporting of its phase 1 / 2 trial which was presented at a conference but has not been published in a peer-reviewed journal that I can find. They make this statement: “the study was not powered for efficacy outcomes.” but go on to report the appearance of efficacy in their press releases. Since one primary end-point is not reported on and since we don't know the baseline characteristics of the treated vs placebo groups, efficacy interpretation with small N's can be misleading. That was the main complaint of the SA “hit piece”. It may be valid. Finally, Mesoblast has announced an EAP while Athersys has said on their CC they will not be offering one. In this settiing an EAP is good for dying patients with no other hope imo, especially since these trials can take awhile. Athersys needed 3 ½ years to do their 36-patient phase 1 / 2, for example. I continue to believe that having a full BLA submitted to the FDA, a partner announced, a superior financial position, a stronger scientific, manufacturing and IP base, a smaller number of patients needed for the Covid-19 trial and an EAP puts Mesoblast in a superior position.