Ann: Rexlemestrocel Reduces Heart Attacks/Strokes/CV Death in CHF, page-385

Thanks for re-posting some of what I wrote on the Yahoo board earlier. Unfortunately, one post was deleted for unknown reasons by the Yahoo censor, and I don't have a copy of it. But as I recall, there was some confusion on the Yahoo board because the language at clinicaltrials.gov refers to the primary endpoint as "time to a CHF-MACE event". The discussion centered around what that means... it's not really defined in the clinical trial description. So, people were confusing a "decompensated CHF event" with a "MACE" event - as they are defined in the press releases. Doubt if there's such confusion on this board, but these are 2 independent non-overlapping categories of "events", imo.

I made the point that "decompensation" refers to events and not stage of disease, which is accounted for by assignment to an NYHA class. Most patients with CHF are outpatients who are walking and wheeling about amongst us "compensated" whether NYHA class 2 or 3. The do fairly well with accommodation, it's a chronic condition, but occasionally they "decompensate", become short of breath (due to lungs filling with edema fluid) and have to go to the ER. If severe enough they get admitted for IV diuretics, medication adjustments, rule out MI/other things, tune up of electrolytes, etc. Generally, they are discharged home after a couple of days. Sometimes that sort of problem occurs because the patient forgot to take his pills at home or ate too much salty fried foods at a party/picnic. It reflects underlying weakness of the cardiac muscle. Those types of events were chosen as a primary endpoint, a surrogate marker for the slowly failing cardiac muscle. Rex-L apparently had minimal impact on those "inotropic" events. A totally different category is patients who go to the ER for a vascular "ischemic" event such as stroke or MI - or to the morgue for either one. Another category would be mortality from some apparently unrelated cause such as an automobile accident that might have something to do with the patient's CHF or not. In any event, the study catalogs all events leading to hospitalization or death. All categories are independent and non-overlapping. Analysis is then done to determine if rex-L impacted the likelihood of falling into any particular category. And surprise, it had a big impact on the categories involving vascular ischemic events. SI labeled it a "major breakthrough" in his presentation to Wainwright. I'm looking forward to seeing the full dataset published in a major medical journal. The most significant difference I see between the December PR and the January PR is the definition of a composite 3-point MACE end point that showed statistical significance across the entire trial. That's an end point that could substitute as a primary end point. Meeting planned with the FDA to discuss a pathway to approval. Let's see what they say.

Finally, I find it interesting that the end-stage CHF trial involving class 4 and LVAD patients showed a comparable "inotropic vs vascular" pattern. Little apparent impact from rex-L on the underlying CHF, but a definite efficacy signal on a different type of vascular problem: Gatro-intestinal bleeding (at least in the LVAD cases). I believe Rex-L has an orphan drug designation for that indication with the FDA and that the company is continuing to collect long-term data on those patients. Another possible point of discussion at the FDA meeting? glta