2. Pharmacokinetic and pharmacodynamic equivalence of Biocon's biosimilar insulin N with US-licensed Humulin® N formulation in healthy subjects: Results from the RHINE-2 (Recombinant Human INsulin Equivalence-2) study
- Jan 23rd, 2023
- Grit Andersen MD, Gursharan Singh PhD, Sundara Moorthi Nainar Murugesan PhD, Rajesh Gogineni MPharm, Nirant Sharma MSc, Jayanti Panda MPharm, Ashwani Marwah MSc, Subramanian Loganathan MD, Sandeep N. Athalye MD
Abstract –
Aim: To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar Insulin N (Biocon’s Insulin-N; Biocon Biologics Ltd., Bangalore, India) and US-licensed Humulin® N (Humulin-N; Eli Lilly and Company, Indianapolis, IN, USA) in healthy subjects.
Materials and methods: This was a phase-1, single-centre, double-blind, randomized, three-period, six-sequence, partially replicated, crossover, 24-h euglycaemic clamp study. Overall, 90 healthy subjects were randomized, of whom 85 completed the study. The subjects received either two single doses of Biocon’s Insulin-N and a single dose of Humulin-N or two single doses of Humulin-N and a single dose of Biocon’s Insulin-N subcutaneously at a dose of 0.4 IU/kg. The primary PK endpoints were the area under the insulin concentration-time curve from 0 to 24 h (AUCins.0-24h) and the maximum insulin concentration (Cins.max). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 h (AUCGIR.0-24h) and the maximum GIR (GIRmax).
Results: Biocon’s Insulin-N was found to be equivalent to Humulin-N for the primary PK (geometric 90% confidence interval for the least squares mean ratio: AUCins.0-24h, 100.98%-115.66% and Cins.max, 95.91%-110.16%) and PD endpoints (intra-subject variability ≥0.294; 95% upper confidence interval [(μT – μR)2 − θσ2WR] <0; point estimates of geometric least squares mean ratio: AUCGIR.0-24h, 104.61% and GIRmax, 100.81%). The safety profile of Biocon’s Insulin-N was similar to that of Humulin-N, and no serious adverse events were reported.
Conclusion: PK and PD equivalence was shown between Biocon’s Insulin-N and Humulin-N in healthy subjects, and both treatments were well tolerated and considered safe.
Conflict of interest statement: GA is an employee of Profil, Neuss, Germany. GS, AM, JP, SL and SNA are employees of Biocon Biologics Ltd and hold stocks in Biocon. NS is an employee of Biocon Biologics Ltd. SMNM is no longer employed by Biocon Biologics Ltd.
