A phase 1 study in Japan found similar pharmacokinetic (PK) and glucose pharmacodynamic (PD) parameters between the biosimilar SAR342434 (SAR-Lis, Sanofi) and the Japan-reference insulin lispro (Humalog) in healthy male participants.

Insulin lispro is a rapid-acting insulin analog used to treat adults and children with type 1 and type 2 diabetes. SAR-Lis was the first insulin lispro biosimilar authorized in the European Union in 2017 and in Japan in 2020. Although similar PK and PD parameters, efficacy, safety, and immunogenicity have been demonstrated between SAR-Lis and the US and EU reference products, Japan’s regulatory guidelines require that PK and PD similarity be shown between the biosimilar and the Japanese reference product.

The randomized, double-blind, crossover study included 36 healthy male participants. Following a single subcutaneous dose of SAR-Lis or the reference product, a euglycemic clamp held blood glucose stable for 10 hours, and the glucose infusion rate (GIR) required to maintain the stable glucose concentration was recorded. The primary PK endpoints measured were maximum plasma insulin lispro concentration (Cmax) and area under the insulin lispro concentration-time curve (AUC) from time 0 to the time of the last quantifiable data point (AUClast), and primary PD endpoints were area under the GIR-time curve from time 0 to 10 hours (GIR-AUC0-10h) and maximum GIR.

Pharmacokinetic and Pharmacodynamic Parameters “Similar Between Treatments”

For the primary PK and PD parameters, the investigators reported that all geometric mean ratios were close to 1, and the corresponding 90% confidence intervals (CI) for PK endpoints and 95% CIs for PD endpoints were within the equivalence range of 0.80 to 1.25. The geometric mean ratios were 0.99 (90% CI, 0.93-1.05) for Cmax, 1.00 (90% CI, 0.97-1.02) for AUClast, 1.07 (95% CI, 0.99-1.15) for GIR-AUC0-10h, and 1.07 (95% CI, 1.00-1.15) for GIRmax. Confidence intervals for secondary PK endpoints (AUC from time 0 to infinity, time to Cmax, and terminal half-life) also fell within bioequivalence margins of 0.80 to 1.25.

SAR-Lis and the Reference Product Were Well Tolerated

The authors reported no serious adverse events (AEs), AEs of special interest, or treatment-emergent AEs (TEAEs) leading to treatment discontinuation. Three mild or moderate TEAEs occurred, 2 after administration of the biosimilar and 1 after the reference product. None of these were considered related to the study medication. The authors also reported “few potentially clinically significant abnormalities in laboratory tests and ECG parameters, with no notable difference between SAR-Lis and [the reference product].”

The investigators concluded that the biosimilar and reference product “showed similar PK exposure profiles and PD potency” in healthy Japanese males, consistent with previous evidence in US and EU populations and providing evidence in support of the use of SAR-Lis as an insulin lispro biosimilar.

Reference

Shiramoto M, Yoshihara T, Schmider W, Takahashi Y, Nowotny I, Kajiwara M, Muto H. Similar pharmacokinetics and pharmacodynamics of biosimilar SAR342434 insulin lispro and Japan-approved Humalog insulin lispro in healthy Japanese subjects. Clin Pharmacol Drug Dev. 2022;11(6):754-760. doi:10.1002/cpdd.1068