Stable High-Concentration Monoclonal Antibody Formulations Enabled by an Amphiphilic Copolymer Excipient

Monoclonal antibodies (mAbs) are a staple in modern pharmacotherapy. Unfortunately, these biopharmaceuticals are limited by their tendency to aggregate in formulation, resulting in poor stability and often requiring low concentration drug formulations. Existing excipients designed to stabilize formulations are often limited by their toxicity and tendency to form particles such as micelles. Here, the ability of a simple "drop-in," amphiphilic copolymer excipient to enhance the stability of high concentration formulations of clinically relevant mAbs without altering their pharmacokinetics or injectability is demonstrated. Through interfacial rheology and surface tension measurements, it is demonstrated that the copolymer excipient competitively adsorbs to formulation interfaces. Further, through determination of monomeric composition and retained bioactivity after stressed aging, it is shown that this excipient confers a significant stability benefit to high concentration antibody formulations. Finally, it is demonstrated that the excipient behaves as an inactive ingredient, having no significant impact on the pharmacokinetic profile of a clinically relevant antibody in mice. This amphiphilic copolymer excipient demonstrates promise as an additive to create stable, high concentration antibody formulations, thereby enabling improved treatment options such as a route-of-administration switch from low concentration intravenous (IV) to high concentration subcutaneous (SC) delivery while reducing dependence on the cold chain.