Denosumab biosimilar (Qilu Pharma)

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

This study was conducted to explore the tolerance, variability, pharmacokinetics (PK), and pharmacodynamics (PD) of denosumab biosimilar (QL1206) in healthy Chinese subjects.

This is a randomized, double-blind, two-arm, parallel study performed to examine the bioequivalence of denosumab biosimilar, QL1206, with that of Xgeva^® (Denosumab) as a reference drug. A single dose of 120 mg/kg of the denosumab biosimilar or Xgeva^® was administered to the subjects, who were followed up for 134 days.

Similar PK properties as those of Xgeva^® were exhibited by QL1206. When compared to QL1206 with Xgeva^®, the 90% confidence intervals of the ratios for C_max, AUC_0-t, and AUC_0-∞ were observed to be within 80-125%. The inter-subject variability (inter-CV) ranged from 29% to 39.5%. Six and three subjects in the QL1206 and Xgeva^® groups were found to be positive for the ADA and negative for the NAb, respectively. The CTX1 concentration-time profiles appeared similar (about 80% decrease from 48 hours to134 days) between the QL1206 and Xgeva^® groups. Adverse events (AEs) were observed in 92.6% and 93.4% of subjects in the QL1206 and Xgeva^® groups, respectively. Reduction in blood calcium level was found to be the most common AE recorded, with an incidence of 72.8% versus 72.4% in the QL1206 and Xgeva^® groups, respectively.

Similar PK and PD characteristics were exhibited by QL1206 as compared to those of Xgeva^®. The inter-CV was slightly large. The safety profiles of denosumab biosimilars and Xgeva^® were found to be similar.