Biocon’s Biosimilar Insulin Demonstrates PK, PD Equivalence to Humulin

The third in a series of clinical studies evaluating pharmacokinetics (PK) and pharmacodynamics (PD) of Biocon’s recombinant human insulins compared to their reference products, the Recombinant Human INsulin Equivalence-3 (RHINE-3) study found PK and PD equivalence between Biocon's Insulin-70/30 and Humulin-70/30. The investigators said both treatments were well-tolerated, and there were “no clinically relevant differences in the safety profiles” between the 2 treatments.

They expect that the biosimilar will be able to “provide reliable and affordable access to patients who are candidates for premixed-insulins.” Premixed insulins combine short-, intermediate-, and/or long-acting insulins to increase the convenience of dosing compared to basal-bolus insulin therapy, which requires at least 4 daily injections.

For patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) who require insulin daily, premixed insulins improve compliance, according to the authors, and usually require only 2 daily injections. Both the reference product and biosimilar 70/30 insulin products investigated in this study contain 70% intermediate-acting and 30% short-acting insulins.

The authors noted that rising insulin costs have made access more difficult for patients with diabetes, “especially mid- to low-income individuals, those on high deductible health plans, or those who are uninsured.” They cited research suggesting that approximately 1 fourth of US patients with diabetes ration their insulin because of the high cost. Biosimilar insulins could provide a lower-cost alternative, they said, especially now that the FDA has changed insulin’s status from a drug to a biologic, which “could facilitate approval of biosimilar insulins in the United States, enabling a competitive market.”

Plasma insulin concentrations and glucose infusion rates (GIRs) were assessed over 24 hours in 74 healthy subjects who received a single dose of the biosimilar and reference product in random order.

The primary PK endpoints were the area under the insulin concentration-time curve from 0 to 24 hours (AUCins.0-24h) and maximum insulin concentration (Cins.max). The primary PD endpoints were the area under the GIR time curve from 0 to 24 hours (AUCGIR.0-24h) and maximum GIR (GIRmax).

Confidence Intervals Were Within the Equivalence Margins for Ratios of Primary PK and PD Endpoints

The 90% CI for the geometric mean ratios of the biosimilar to the reference product were within the 80% to 125% equivalence range for both PK endpoints (95% CI, 89.2-97.4 for AUCins.0-24h; 95% CI, 88.3-97.9 for Cins.max). Confidence intervals for the primary PD endpoints were also within the equivalence margins (95% Ci, 84.2-96.1 for AUCGIR.0-24h; 95% CI, 86.0-98.5 for GIRmax).

Although secondary PK and PD endpoints were not required to meet equivalence criteria, the authors commented that several secondary endpoints did: AUCins.0-2h, AUCins.0-6h, AUCins.0-12h, AUCins.12-24h, AUCins.0−infinity, AUCGIR.0-6h, AUCGIR.0-12h, and AUCGIR.12-24h.

The investigators added that the quality of the euglycemic clamp was considered good and comparable between treatments. Regarding safety, there were 43 treatment-emergent adverse events (TEAEs), 21 associated with the biosimilar and 18 with the reference product. Headache and hematoma were the most frequently reported TEAEs. There were no serious AEs, deaths, or discontinuations due to safety or tolerability reasons.

Reference

Plum-Mörschel L, Klein O, Singh G, et al. Pharmacokinetic and pharmacodynamic equivalence of Biocon's biosimilar Insulin 70/30 with US-licensed HUMULIN^® 70/30 formulation in healthy subjects: results from the RHINE-3 (Recombinant Human INsulin Equivalence-3) study. Diabetes Obes Metab. 2022;24(9):1819-1828. doi:10.1111/dom.14768