Ann: Remestemcel-L for COPD Published in Respiratory Research, page-46

parts that create to me very bad impression(my highlights)


1- We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels.


2- n COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups.

3- In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases.

4- There was no change in number of COPD exacerbations over the 2 year study period between remestemcel-L- vs placebo-treated patients when stratified for CRP ≥ or < 4 mg/dl (Table 3).Fig. 3

5- The biological rationale for investigation of potential salutary effects of MSCs in COPD is based on the premise that secretion of multiple paracrine factors including anti-inflammatory cytokines and growth factors that thereby facilitate tissue repair may counter or potentially even reverse chronic inflammation and lung destruction. However, studies to date of MSC administration in COPD patients have consistently demonstrated safety but not efficacy [5,6,7,8].

My note: >>> (that item 5- matches with FDA concerns and comments)


CATO