805-P: Development of a Semaglutide-Releasing Long-Acting Injectable, IVL3021, and Its Physicochemical and Pharmacokinetic Studies

For many chronic conditions, microsphere-based long-acting injectables (LAIs) have been employed to replace repetitive daily or weekly therapies with long-term therapies (e.g. 1 month). The key technology to develop LAIs is controlling release profiles since it is significant not only to patient adherence and efficacy but also to the safety of the medications by minimizing the burst exposure of the drug and keeping its drug level within the therapeutic range. The focus of the current study is on semaglutide (Sema), an FDA-approved glucagon-like peptide-1 (GLP-1) receptor agonist for managing diabetes and obesity. Most annoying adverse events that Sema induces are gastrointestinal AEs, which can be mitigated by using LAIs. However, encapsulating it into microparticles and controlling the release have presented challenges, given its physicochemical properties. In this study, we introduce a novel one-month LAI of Sema, named IVL3021, developed using IVL-DrugFluidics® technology. This microfluidics-based manufacturing approach enables precise control of drug release through size and morphology-regulated microspheres. Our study demonstrates the smooth uniform spherical morphology of IVL3021 microspheres, with an encapsulation efficiency exceeding 97.0%. Importantly, in preclinical pharmacokinetic studies, IVL3021 maintains plasma concentrations of Sema within the therapeutic range over 4 weeks without an initial burst release.

In conclusion, IVL3021 showed its potential to be used as a 1-month LAI of Sema for obesity and diabetes management. The current study also suggested the potential of IVL-DrugFluidics® Technology in creating size-controlled peptide-encapsulating microspheres. Based on the positive results, further preclinical evaluation is ongoing.