2052-LB: Semaglutide Depot, a Long-Acting Injection of Semaglutide Administered Once Every Four Weeks, Demonstrates Similar Efficacy and PK Profile to Daily Semaglutide Administration

Introduction and Objectives: Semaglutide Depot consists of extended-release microspheres administered every 28 days, aiming to provide improved dosing regimen over the currently available once weekly dose Semaglutide Depot efficacy and PK profile were evaluated in mice and minipigs. The study aimed to assess the efficacy and the PK profile of Semaglutide Depot injected once compared to Semaglutide API daily in mice or every 72 hours in minipigs.

Methods: In the PK study, db/db mice received SC injection of 2mg/kg Semaglutide Depot on day 0 or daily injections of 0.02mg/kg Semaglutide API for 42 days. In a parallel PD study, db/db mice were injected IM with 2mg/Kg Semaglutide Depot on day 0 or daily injections of 0.02mg/kg Semaglutide API, for 28 days. The PK profile, fasting blood glucose, HbA1c levels and feed intake were measured. In the minipigs PK study, animals were injected with 0.5mg/kg Semglutide Depot IM on day 0 or with 0.008mg/Kg Semaglutide API SC once every 72 hours for 28 days.

Results: PK studies in both species demonstrate sustained release profile maintaining plasma concentrations within the therapeutic range for at least 30 days. The PK profile is correlated with PD in mice. Significant reductions in fasting glucose levels at days 14 and 28, as well as HbA1c levels at day 28 in Semaglutide Depot-treated mice were noted, compared with vehicle treated controls. Additionally, feed intake was significantly lower in Semaglutide Depot-treated mice. Notably, a single dose of Semaglutide Depot given on day 0 was comparable to 28 daily doses of Semaglutide API.

Conclusions: Semaglutide Depot given as a single dose on day 0 showed a one-month lasting PK profile and a comparable efficacy to that of Semaglutide API given daily or every 72 hours in mice and minipigs, respectively. Phase I/IIa clinical study is planned to explore Semaglutide Depot bioavailability and efficacy in diabetic patients.