Oral drug delivery as an alternative to needle-based injection for large molecules : an assessment of the field & evaluation of high-priority technologies

Abstract

Oral delivery of large molecules is widely considered the "holy grail" of drug delivery, but attempts to achieve this within the past century have been met with a lack of success, confounded by low bioavailability. Novel mechanisms need to be assessed in order to deliver a clinically relevant amount of drug into systemic circulation, while protecting the drug from pH denaturation and the harsh enzymatic environment of the gut. To assess the field, this thesis evaluates startup companies and academic labs focusing their efforts on the oral delivery of biologics. The holistic, phased analysis of the field includes the following items: ** Value proposition assessment as applicable to Amgen's pipeline; ** Literature review into historical barriers; ** Technology landscape of the current space; ** Down-selection to highly valued technology prospects; ** Risk assessment and mitigation planning activities.

The approach outlined above led to the identification of two promising technologies (Tech A and Tech B) that use novel methods to deliver drug through the lining of the small intestine into systemic circulation. Both early stage technologies hold a significant amount of promise for Amgen if they enable both systemic and localized GI delivery successfully, but have multiple risks to address prior to use as a platform delivery option. Risks that have been prioritized for evaluation include: health concerns over long term damage and infection, low bioavailability, limited payload capabilities, and large final device size. In Silico modeling in COMSOL Multiphysics of the mechanism of action of Technology A and the resultant spread of drug product into the lining of the small intestine was completed as a preliminary test of the risk of low bioavailability.

Results from this model indicate that Technology A can be optimized via nozzle diameter and ejection threshold pressure to deliver liquid drug product into the desired locations within the small intestinal wall for optimal drug uptake into systemic circulation. If these technologies prove to be successful, the resultant product offering could prove highly disruptive in the industry and allow Amgen to revolutionize the manner in which patients interact with their medications.