Adult stem cells help patients with kidney disease
Mesoblast Limited announced that results from the Company's Phase 2 trial in patients with diabetic nephropathy showed that a single infusion of its intravenously delivered allogeneic mesenchymal precursor cell (MPC) product candidate MPC-300-IV was safe, reduced damaging inflammation, and preserved or improved renal function over at least 24 weeks. The results were presented at the 75th annual meeting of the American Diabetes Association (ADA).
The trial's lead investigator, Associate Professor David Packham, Department of Medicine, University of Melbourne, and Director of the Melbourne Renal Research Group, stated that: “The results show that Mesoblast's allogeneic cell therapy was safe and may be particularly useful in patients with moderate to severe diabetic nephropathy, a disease which, despite all existing therapies, continues to have a high rate of progression to dialysis or transplantation, and to portend a high risk of death from cardiovascular disease."
Diabetic nephropathy affects 40-50% of patients with type 2 diabetes and accounts for about 40% of all patients with end-stage renal disease (kidney failure). It is thought to be caused by ongoing monocyte inflammation and endothelial dysfunction (abnormal blood vessels) in the kidneys.
Mesoblast's bone marrow-derived MPCs are potent modulators of monocyte inflammation, and have been shown in preclinical studies to reduce monocyte infiltration in diabetic kidneys and to reverse endothelial dysfunction. Consequently, Mesoblast is developing MPC-300-IV for intravenous delivery in the treatment of diabetic nephropathy.
MPC-300-IV was evaluated in a double-blind, randomized, placebo-controlled, doseescalating Phase 2 trial of 30 patients with type 2 diabetes and moderate to severe renal impairment, stage 3b-4 chronic kidney disease (CKD), who were already on a stable regimen of the standard of care therapy for diabetic nephropathy (renin-angiotensin system inhibition with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers).
Patients received a single infusion of 150 million MPCs, 300 million MPCs, or saline control. The objectives of the trial were to evaluate safety and to explore potential efficacy signals of MPC treatment on renal function.
The pre-specified primary efficacy endpoint was to evaluate effects of MPC treatment relative to placebo on renal functional decline at 12 weeks, as defined by change in glomerular filtration rate (GFR) measured both by direct isotope scan and by serum-creatinine based estimation, and then for an additional 48 weeks of follow-up. Pre-specified secondary analyses included GFR differences between treatment and placebo groups with baseline GFR>30ml/min/1.73m2 (stage 3b CKD, accounting for 60% of enrolled patients), and treatment-related effects on the monocyte-derived cytokine interleukin-6 (IL- 6), a major inflammatory marker associated with renal failure progression and adverse cardiovascular outcomes.
The primary efficacy endpoint of decline or change in GFR was in line with the 2012 joint workshop held by the United States Food and Drug Administration and the National Kidney Foundation which recommended that time to 30%-40% decline in GFR is an acceptable primary endpoint for evaluating potential benefits of new therapies for this patient population (Levey et al. GFR decline as an endpoint in clinical trials for CKD. American Journal of Kidney Disease 2014:64(6):821-835).
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