Cell Therapy News/Articles, page-13676

My 2 cents:

1. Rex-L is a needed add-on to current standard of care (SOC) treatment as it has a clinically meaningful and statistically significant reduction in Majore Adverse Cardiac Events (MACE). Because current SOC treatments treat fluid overload and decrease recurrent hospitalisaitons somewhat adequately - personally I am not as concerned that Rex-L has no additional effect on recurrent hospitalisations.
2. The fact that recurrent hospitalisations alone are correlated with death, and that placebo and treatment groups had the same incidences of recurrent hospitalisations, tells me that Rex-L has a unique multimodal mode of action (MOA) in further reducing MACE compared to SOC.
3. A simple model of the progression of Heart Failure with Reduced Ejection Fraction (HFrEF) severity has multimodal inputs that align well with Rex-L proposed MOA:

a) Treating cardiac and systemic inflammation
b) Stabilising endothelial dysfunction (i.e. plaque)
c) Reducing maladaptive left ventricular (LV) remodeling - via reducing remodeling following myocardial infarction (MI).

To circle back, Rex-L is showing to be a much needed add on to current SOC treatment and is involved in many aspects of CHF progression. In the next trials it would be interesting if a reclassification is conducted at the end of the trial duration to see (or confirm my thoughts) if indeed Rex-L halts the progression of Class II to Class III (as in line with reducing the death rates of class III to class II outcomes). There is a good argument on paper that this would be the case (however needs to be confirmed by the next trial - if and only if this is of importance to clinicians).

One more point, it would be interesting to see if multiple doses (albeit a single dose has lasting effects) has even greater benefits in terms of reducing MACE, halting disease progression (and possibly reducing repeat hospitalisations above the SOC) also due to the pathological memory of a series of stress responses in the chronically inflamed heart [substitute multiple doses for the chronically inflamed GI tract for crohns].

Let's hope the FDA see that Rex-L safely meets the unmet clinically important need for reducing MACE outcomes for CHF patients, and provides a pathway for a confirmatory Phase IV trial to benefit this extraordinary large patient population in need.