Subcutaneous delivery of monoclonal antibodies: How do we get there?

The convenience of subcutaneous (SC) administration and the increasing interest in monoclonal antibody (mAb)-based therapies for chronic diseases, hint their potential for SC delivery in a near future. In addition, there is a common interest among patients, clinicians and pharmaceutical industry in moving from intravenous to SC administration of mAbs due to benefits of improved patient compliance and reduced costs to the healthcare system. Despite the wide use of this route of administration in diseases like diabetes and rheumatoid arthritis, SC bioavailability of mAbs has been shown to be incomplete and variable in most preclinical and clinical studies. This evidences a gap in the understanding of SC absorption process of mAbs and in their drug development process. Likewise, challenges present in drug formulation, such as high viscosity and aggregation, and the inherent immunogenicity of mAbs have also been hampering the successful translation to clinical settings. This review provides a characterization of the subcutaneously delivered mAbs that have entered the market in the last 10 years as well as a snapshot of the landscape of currently undergoing clinical trials. Moreover, there is an overview of the factors influencing SC absorption of mAbs and the preclinical models in use to study SC pharmacokinetics. Considerations about drug formulation and immunogenicity of mAbs are also explored. Subcutaneous delivery of monoclonal antibodies presents several challenges during drug development process, such as drug formulation, immunogenicity, pharmacokinetic assessment during preclinical stage and translation into clinical practice. [Display omitted]