Dulaglutide Biosimilar LY05008 Demonstrates Therapeutic Equivalence in Phase 3 Trial for Type 2 Diabetes
核心洞察
LY05008, a dulaglutide biosimilar developed by Boan Biotech, achieved equivalent efficacy to the reference product in reducing HbA1c levels by approximately 1.44% versus 1.41% at 24 weeks in Chinese adults with type 2 diabetes.
The phase 3 randomized trial enrolled 440 patients and demonstrated comparable safety profiles between LY05008 and dulaglutide, with similar rates of treatment-emergent adverse events at 91% and 89.9% respectively.
Both treatments showed significant reductions in fasting plasma glucose, postprandial glucose, and body weight, with no statistically significant differences between groups across all secondary endpoints.
LY05008 (BA5101), a biosimilar to the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide, has demonstrated therapeutic equivalence to its reference product in a phase 3 clinical trial involving Chinese adults with type 2 diabetes mellitus (搜索). The study, published in the Journal of Diabetes, showed that the biosimilar developed by Boan Biotech achieved comparable efficacy, safety, and immunogenicity profiles to dulaglutide (Trulicity; Eli Lilly & Co).
Clinical Trial Design and Patient Population
The multicenter, randomized, open-label, active comparator phase 3 study enrolled 440 Chinese adults with type 2 diabetes whose condition was inadequately controlled by metformin alone. Patients were randomly assigned to receive either LY05008 (n = 222) or dulaglutide (n = 218) as a 1.5-mg subcutaneous injection once weekly for 24 weeks.
The study population was predominantly male (59.1%), with comparable baseline characteristics between groups. The LY05008 group had a mean age of 52.9 years, while the dulaglutide group averaged 52 years. Baseline HbA1c levels were similar across both groups, with approximately 56% of patients having HbA1c levels below 8.5%.
Primary Efficacy Results
The trial's primary endpoint was the mean change in HbA1c from baseline to week 24. Results demonstrated equivalent efficacy between the two treatments, with mean HbA1c reductions of -1.44% for LY05008 and -1.41% for dulaglutide (95% CI -0.08, 0.19; P > .05). The difference in least square mean change between groups was 0.06%, falling within the predefined equivalence margin of -0.4% to 0.4%.
At the 12-week interim analysis, both groups showed significant HbA1c reductions of -1.47% for LY05008 and -1.39% for dulaglutide (P > .05), confirming early therapeutic benefit.
Glycemic Control Targets
The proportion of patients achieving clinically meaningful HbA1c targets was comparable between groups. At week 12, approximately 40.1% of LY05008 patients and 42.2% of dulaglutide patients achieved HbA1c levels of 6.5% or less, while 60.4% and 60.6% respectively reached levels below 7%.
By week 24, these proportions remained similar, with 41.0% of LY05008 patients and 43.6% of dulaglutide patients achieving HbA1c ≤6.5%, and 55.9% versus 66.5% reaching HbA1c <7%.
Secondary Endpoints
Both treatments demonstrated significant improvements across secondary endpoints. For fasting plasma glucose levels, mean changes from baseline to weeks 12 and 24 were -2.578 and -2.222 mmol/L for LY05008, compared to -2.681 and -2.690 mmol/L for dulaglutide (P > .05).
Postprandial glucose levels showed similar reductions, with 2-hour PPG changes of -4.364 and -4.800 mmol/L for LY05008 versus -3.502 and -4.217 mmol/L for dulaglutide at weeks 12 and 24 respectively (P > 0.05).
Weight reduction was observed in both groups, with LY05008 patients losing an average of 2.01 kg at week 12 and 2.68 kg at week 24, compared to 1.71 kg and 2.42 kg respectively in the dulaglutide group (P > .05).
Safety and Tolerability Profile
The safety profiles of LY05008 and dulaglutide were comparable throughout the study period. Treatment-emergent adverse events occurred in 91% of LY05008 patients versus 89.9% of dulaglutide patients, with drug-related adverse events reported in 57.7% and 61.5% respectively.
The most common adverse events in both groups included decreased appetite, diarrhea, upper respiratory tract infection, hyperuricemia, nausea, urinary tract infection, and vomiting. Most events were mild to moderate in severity with no significant differences between groups.
Hypoglycemic events were infrequent, occurring in 0.9% of LY05008 patients compared to 3.7% of dulaglutide patients. Serious adverse events were reported in 4.1% of LY05008 patients versus 3.7% of dulaglutide patients.
Pharmacokinetics and Immunogenicity
Trough plasma concentrations at steady state were comparable between LY05008 and dulaglutide groups, confirming similar pharmacokinetic profiles. Immunogenicity assessment revealed minimal antidrug antibody formation, with only one patient in the LY05008 group testing positive for neutralizing antibodies.
Regulatory Status and Clinical Implications
LY05008 has been granted marketing authorization in China under the brand name Boyouping (搜索). The development of this biosimilar followed established regulatory guidelines, with preclinical studies demonstrating high similarity to dulaglutide in physicochemical and functional properties, and phase 1 trials confirming pharmacokinetic similarity.
"In Chinese patients with T2DM following multiple subcutaneous injections, efficacy equivalence was achieved between LY05008 and dulaglutide with respect to change from baseline in HbA1C reduction to week 24," the study authors concluded. "Comparable effects in safety and immunogenicity profiles were observed between the 2 groups."