Novel MSC therapy appears safe and effective in preventing decline in eGFR

Safety and efficacy of cell treatment with cryopreserved CD362-selected allogeneic bone marrow mesenchymal stromal cells (MSCs) was established in patients with type 2 diabetes (T2D) and progressive chronic kidney disease (CKD). Over an 18-month period, the rate of decline of estimated glomerular filtration rate (eGFR) was lower for patients treated with this new modality [1].

Dr Matthew Griffin (University of Galway, Ireland) explained that MSCs simultaneously target multiple pathways of diabetic kidney disease (DKD). In the multicentre, randomised, placebo-controlled, phase 1b/2a NEPHSTROM study (NCT02585622), cryopreserved CD362-selected allogeneic bone marrow MSCs (ORBCEL-M) were investigated. The aim was to establish the safety and tolerability of a single IV infusion of allogeneic ORBCEL-M in patients with T2D and progressive CKD. The protocol was designed to include 48 adult patients with T2D and CKD between the ages of 40 and 85 years. Cohort 1, of which the results are presented, included 12 patients who received ORBEL-C 80 x 10⁶ NEPHSTROM ORBEL-C and 4 patients received placebo. Total follow-up was 18 months. All participants were male with those in the ORBCEL-M group were marginally older. The proportion of serious adverse events was similar in both groups (see Table).

Table: Safety profile outcomes MSC therapy



Serial serum assays (multi-antigen bead Luminex) for anti-HLA antibodies indicated low-level sensitisation against Class I HLA in 1 subject from month 3.AE, adverse event; HLA, human leukocyte antigen; MSC, mesenchymal stromal cell; SAE, serious adverse event.

The annual rate of renal functional decline from baseline to 18-month follow-up showed an eGFR (CKD-Epidemiology Collaboration equation) of −2.6 with ORBCEL-M versus −8.7 with placebo (P=0.034) and an eGFR (Modification of Diet in Renal Disease equation) of −2.4 with ORBCEL-M versus −8.1 for placebo (P=0.034). “A potentially interesting observation was that the preservation of regulatory T cell numbers in ORBCEL-M-treated patients remained stable compared to the placebo-treated patients, especially in the first 6 months,” Dr Griffin said. “Total and memory Tregs correlated with serum levels of inflammatory mediators as well as with eGFR in the overall DKD cohort.”

1. Griffin MD, et al. Safety and Preliminary Efficacy Results of a Novel Mesenchymal Stromal Cell Therapy in Diabetic Kidney Disease: The Multicenter, Randomized, Placebo-Controlled, Phase-1b/2a NEPHSTROM Clinical Trial. FR-OR40, ASN Kidney Week 2022, 3–6 Nov.

 

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Posted on 8 December, 2022