Efficacy and Safety of Dulaglutide Biosimilar LY05008 Versus the Reference Product Dulaglutide (Trulicity) in Chinese Adults With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Active Comparator Study.

backgroundDulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been approved for improving glycemic control and reducing the risk of cardiovascular (CV) adverse events. A previous result in healthy Chinese male subjects demonstrated the pharmacokinetic (PK) similarity of LY05008 and the licensed product dulaglutide, with comparable safety and immunogenicity profiles. A well-controlled phase 3 study with an adequate sample size was subsequently conducted for safety and efficacy evaluation.

methodsIn a multicenter, randomized, open-label, active comparator phase 3 study, Chinese adults diagnosed with type 2 diabetes mellitus (T2DM) were randomly assigned 1:1 to receive a subcutaneous injection of 1.5 mg LY05008 or dulaglutide once weekly for 24 weeks. The primary endpoint was the mean change in HbA1c from baseline to Week 24. The secondary endpoints included the mean change in HbA1c from baseline to Week 12; the proportion of patients who had achieved HbA1c ≤ 6.5% at Weeks 12 and 24; and the mean change in body weight, fasting plasma glucose (FPG) level, and 2-h postprandial plasma glucose (PPG) level from baseline to Weeks 12 and 24. Safety, PK, and immunogenicity profiles were also included for data analysis.

resultsA total of 440 patients were randomized to receive LY05008 (n = 222) or dulaglutide (n = 218). The mean changes in HbA1c from baseline to Week 24 in the LY05008 group and dulaglutide group were -1.44% and -1.41%, respectively, with a least square mean difference (LSMD) and 95% confidence interval (CI) of 0.06% (-0.08, 0.19) (p > 0.05). Efficacy equivalence could be demonstrated since the 95% CI between the reference drug and a biosimilar fell entirely within the range of (-0.4%, 0.4%). The mean changes in HbA1c from baseline to Week 12 in the LY05008 group and dulaglutide group were -1.47% and -1.39% (p > 0.05), respectively. At Week 12, 40.1% of patients who received LY05008 and 42.2% of those who received dulaglutide had a decrease in the HbA1c level to 6.5% or less, and 60.4% and 60.6% of patients in the LY05008 group and the dulaglutide group had a decrease in the HbA1C level < 7%, respectively. At Week 24, 41.0% and 43.6% of patients achieved an HbA1c ≤ 6.5%. 55.9% and 66.5% of patients in the LY05008 group and the dulaglutide group achieved the HbA1c goal of < 7%, respectively. The mean changes in body weight from baseline to Weeks 12 and 24 in the LY05008 group and dulaglutide group were -2.01 and -1.71 kg (p > 0.05) and -2.68 and -2.42 kg (p > 0.05), respectively. The mean changes in FPG level from baseline to Weeks 12 and 24 in the LY05008 group and dulaglutide group were -2.578 and -2.681 mmol/L (p > 0.05) and -2.222 and -2.690 mmol/L, respectively. In the LY05008 group and the dulaglutide group, the mean changes in 2-h PPG levels from baseline to Weeks 12 and 24 were -4.364 and -4.800 mmol/L(p > 0.05) and-3.502 and -4.217 mmol/L (p > 0.05), respectively. The common treatment emergent adverse events (TEAEs) in the LY05008 and dulaglutide groups were decreased appetite, diarrhea, upper respiratory tract infection, hyperuricemia, nausea, urinary tract infection, and vomiting. Most TEAEs were mild to moderate in severity. No significant differences were observed between the groups in terms of TEAEs. Hypoglycemic events were noted in 0.9% of patients who had received LY05008 and in 3.7% of those who had received dulaglutide. Serious adverse events were reported in 4.1% of patients in the LY05008 group and in 3.7% of patients in the dulaglutide group. The PK parameter C

conclusionThe primary endpoint was met in this study through the demonstration of equivalent efficacy in HbA1c reduction in Chinese adults with T2DM between LY05008 and dulaglutide. Overall, the biosimilar product LY05008 showed comparable safety, PK, and immunogenicity profiles against the reference drug dulaglutide.

trial registrationClinicalTrials.gov identifier: CTR20221721.