Accelerating the development of biotherapeutics for subcutaneous delivery

Injection under the skin (termed 'subcutaneous' injection) is a well-established and well-tolerated route of administration of certain drugs that cannot be swallowed as tablets or capsules. These include highly effective drugs based on large and fragile molecules, such as peptides and proteins (termed 'biotherapeutics'), including insulin. These drugs are extensively degraded by the acid and enzymes present in the gut, in addition to being very poorly absorbed across the gut wall. Subcutaneous injection offers important advantages over intravenous (directly into the vein) administration of biotherapeutics, including the convenience of self-administration, improved patient experience and safety profile. Although subcutaneous injection of biotherapeutics is well-established, there remain important gaps in knowledge, which are hindering progress in the field. This is particularly the case with biotherapeutic drugs that are designed to be released slowly after subcutaneous injection; such 'slow release' injections are designed to reduce the frequency of drug administration, improving patient convenience. These gaps in knowledge could be addressed effectively by the creation of a laboratory model enabling the study of subcutaneous injection and prediction of its efficacy in humans. Such a model would significantly facilitate the development of highly effective slow-release biotherapeutics for subcutaneous injection for a range of diseases.

Astra Zeneca possess a portfolio of novel slow-release biotherapeutics for subcutaneous injection. These are in early phase development and require extensive testing and optimisation in order to progress into further development and eventually into marketed drugs. However, this process is made difficult due to the absence of a suitable laboratory model to study subcutaneous injection. This project will initially develop a laboratory model of injection site, which is designed to predict the efficacy of new drugs (biotherapeutics) for subcutaneous injection. We will validate the newly developed model by comparing with data in humans, ensuring its reliability in predicting outcomes in humans. The model will then be used to study a large number of products in development, helping us to identify key product attributes which result in desirable performance in humans. Identification of these key product attributes will in turn help us improve products in development. The project will therefore facilitate rapid and cost-effective development of new drugs, namely biotherapeutics for subcutaneous injection.