Efficacy and Safety of MT1013 in Patients with Secondary Hyperparathyroidism Undergoing Maintenance Dialysis

Background: MT1013 is a first-in-class dual-agonist of the calcium-sensing receptor (CaSR) and osteogenic growth peptide (OGP) developed by Shaanxi Micot Technology Co., Ltd, indicating to treat patients with secondary hyperparathyroidism (SHPT) undergoing maintenance dialysis. Beyond CaSR, MT1013 constitutes an additional target OGP, which can regulate the differentiation of mesenchymal stem cells into osteoblasts and thus promote bone formation. Methods: A phase II trial (NCT06747247) was initiated in China for MT1013, including Part A, B and C; here we reported results of Part C which aim to investigate safety and efficacy of IV MT1013 in patients with SHPT on maintenance hemodialysis. All patients received IV MT1013 three times a week after hemodialysis for 52 weeks, with primary endpoint proportion of subjects with iPTH level decreased＞30% compared to baseline. Results: A total of 33 patients were enrolled in the study. Percentage of subjects who achieved＞30% decrease in iPTH at W24 and W52 compared with baseline level were 87.5% and 89.7% respectively; the percentage of subjects who achieved ＞50% decrease in iPTH were 71.9% and 69%. In the week of W52, 72.4% subjects were with iPTH＜300 pg/ml; efficacy of MT1013 reached “steady state” in iPTH control since Week 9. Bone Mineral Density (BMD) in femoral neck and lumbar spine was significantly improved (p＜0.05) at Week 53; since the inclusion criteria requires a minimal “wash-out” period of cinacalcet only for 8 days, the further improvement of BMD is likely to come from the novel target “OGP”. Bone turnover biomarkers b-ALP, PINP, TRAP-5b, OC and CTX also significantly decreased, suggesting the high-level bone turnover status greatly relieved. MT1013 was well tolerated in CKD-SHPT patients, with no severe TEAE or SAE considered to be related to the study drug, and no new signal was observed beyond the ones identified in other calcimimetics. No gastrointestinal tract relevant adverse reactions were observed in this study. Conclusion: MT1013 presents great efficacy and safety in patients with SHPT undergoing maintenance dialysis. By imposing an additional OGP target beyond traditional CaSR, MT1013 not only controls iPTH but also promotes bone formation, suggesting its potential innovative therapeutic role in those patients.