A Novel Placental Cell Therapy for the Treatment of Diabetic Foot Ulcers with Peripheral Vascular Disease

Introduction: Diabetic foot ulcers (DFU) are a major source of preventable morbidity in adults with diabetes. Consequences of foot ulcers include decline in functional status, infection, hospitalization, lower-extremity amputation, and death. The current treatment of DFUs can only relieve the symptoms but cannot repair damaged blood vessels and nerves. Patients who have DFU with peripheral arterial disease (PAD) have a limited ability to heal compared to patients without PAD. There is an unmet need for the medical treatment of the underlying mechanisms of PAD. A proprietary placental mesenchymal like adherent stromal cells, MLASCs, were evaluated as a potential emerging therapy for DFUs with PAD.Methods: A bilateral hind limb ischemia (HLI) model in diabetic db/db mice was utilized to test blood flow restoration. A placebo-controlled Phase 2 study evaluated safety and efficacy of MLASCs administered intramuscularly in subjects with DFU with and without PAD; The primary efficacy assessment evaluated complete wound closure of the index ulcer, defined as ulcer closure within 3 months after dosing (Visit 8) and retaining wound closure for the subsequent 4 weeks. The primary safety endpoint was the frequency and severity of adverse events.Results:MLASCs delivered intramuscularly in the HLI model promoted angiogenesis, neovascularization, tissue regeneration, immunomodulation, and reduced inflammation. The enhanced restoration of blood flow/collateral blood vessel formation in injured limbs indicated systemic effects. In the placebo-controlled Phase 2 study evaluating safety and efficacy of MLASCs administered intramuscularly in subjects with DFU with and without PAD, primary efficacy endpoint for PAD was 34.3% in MLASC dose groups combined, 38.5% in low cell dose vs 22.6% in placebo group (response was in line with target response of 40%). Overall, the product was well tolerated.Discussion: Treatment with MLASCs was associated with a clinically significant and meaningful difference relative to placebo in the treatment of DFU with PAD. Reduced incidence of de-novo gangrene and delayed time to re-opening of index ulcers was observed in all cell-treated PAD patients compared with placebo. These primary endpoint findings suggest that treatment with MLASC might offer safe and effective treatment of DFU among subjects with PAD.   References:McDermott K, et al. Diabetes Care. 2023 Jan; 46(1): 209–221.