A phase 1 study in China found that pharmacokinetics, safety, and immunogenicity were similar between the liraglutide biosimilar RD12014 and the reference product (Victoza) in healthy male participants.
A phase 1 study in China found that pharmacokinetics (PK), safety, and immunogenicity were similar between the liraglutide biosimilar RD12014 (Sunshine Lake Pharma) and the reference product (Victoza) in healthy male participants. The authors used their findings to support a new drug application in China, which does not currently have a liraglutide biosimilar on the market.
Liraglutide is used to treat type 2 diabetes (T2D), which accounts for more than 90% of diabetes cases. The authors said that the prevalence of the disease is increasing and noted the increased risk of cardiovascular disease, blindness, kidney disease, and other conditions associated with T2D. Because traditional anti-diabetic drugs, such as insulin and sulfonylureas, may cause hypoglycemia, they wrote, “it is necessary to develop new drugs of new mechanisms” to effectively control blood glucose and reduce the risk of complications.
Glucagon-like peptide-1 (GLP-1), according to the authors, reduces blood glucose levels, suppresses glucagon secretion, protects pancreatic beta-cells, slows gastric emptying, and helps reduce body weight. However, since GLP-1 has a short half-life, liraglutide was developed as a longer half-life GLP-1 analog.
The reference product is currently used as a subcutaneous injection to treat T2D. It was approved as an adjunct therapy to diet and exercise for T2D by the European Medicines Agency (EMA) in 2009 and by the FDA in 2010. The reference product was also approved to prevent cardiovascular events in adults with T2D by the FDA in 2017 and by China in 2020.
The investigators said that several biosimilars referencing Victoza are in clinical trials, but there are no liraglutide biosimilars currently on the market in China. Their study evaluated pharmacokinetics, safety, and immunogenicity of the liraglutide biosimilar candidate RD12014 in 49 healthy male participants. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0−last). Subjects received a single dose of either the biosimilar or reference product, followed by a seven-day washout period, and then a single dose of the other biologic.
PK Equivalence Was Demonstrated Between RD12014 and Victoza
The 90% confidence intervals of the geometric mean ratios of Cmax (90% CI, 106-118) and AUC0-last (90% CI, 107-117) for the biosimilar and reference product were within the equivalence range of 80% to 125%.
Overall, the safety profiles of the 2 biologics were similar, the authors said, with 14 adverse events (AEs) occurring in 11 subjects (22%) in the biosimilar group and 19 AEs in 16 subjects (33%) in the reference product group. Thirteen AEs in the biosimilar group and 12 in the reference product group were considered treatment related. All AEs were mild and were resolved without medical intervention by the end of the study. The most common treatment-related AEs were an increase in serum uric acid (12%), and an increase in blood bilirubin (10%), with comparable incidence in the 2 groups. The authors added that there were no major hypoglycemic episodes during the trial, indicating that GLP-1 analogs “reduce blood glucose in a glucose-dependent mode and may even reduce the risk of hypoglycemia.”
Regarding immunogenicity, blood samples from all 49 subjects were negative for anti-drug antibodies, before and after receiving the study drugs.
The investigators concluded their study demonstrated PK similarity of RD12014 to the reference product, with comparable safety and immunogenicity profiles, and added that their findings were used to support a new drug application in China.
Zhou R, Guo L, Gao X, et al. A phase I study comparing the pharmacokinetics of the biosimilar (RD12014) with liraglutide (Victoza) in healthy Chinese male subjects. Clin Transl Sci. 2022;15(10):2458-2467. doi:10.1111/cts.13374