Poor absorption across the gastrointestinal barrier and extensive degradation by proteolytic enzymes interfere with the oral administration of therapeutic peptides. In 2019, an oral tablet form of semaglutide (a glucagon-like peptide-1 (GLP-1) analog, i.e., a GLP-1 receptor agonist) has been approved by the FDA, EMA, and others for the treatment of type 2 diabetes. This GLP-1 receptor agonist is a prescription medication used not only for the treatment of type 2 diabetes in adults, but also for chronic weight management in adults with obesity. Importantly, the approved tablet formulation is taken in the morning under fasting conditions with an interval of 30 minutes prior to food/liquid intake.
Typically, there are several major issues relevant for virtually all of absorption/permeation enhancers. The first and the most important issue is the large intra-subject variability in the efficacy of delivery. Second issue is the requirement for high dosing frequency. Third issue is the large ratio of absorption enhancer carrier to active pharmaceutical ingredient (API, i.e., semaglutide in this case).
For instance, Novo Nordisk currently uses the N-[8-(2-hydroxybenzoyl) aminocaprylate] (SNAC or salcaprozate sodium) as the absorption enhancer, which serves as a carrier for oral delivery of semaglutide, a glucagon-like peptide-1 (GLP-1) analog. Remarkably, Novo Nordisk eliminated the large intra-subject variability in the efficacy of semaglutide delivery (the first issue mentioned above). To achieve this, two important requirements were fulfilled: (i) the GLP-1 analog, semaglutide, with a long half-life was developed; (ii) SNAC absorption enhancer-mediated delivery system was selected . In addition, Novo Nordisk’s researchers found that a subject fasting state is required before and after taking the first-of-its-kind oral semaglutide medicine (Rybelsus®). If all of the above mentioned requirements are met, then there is no large intra-subject variability in the efficacy of oral semaglutide and this was convincingly demonstrated.
The subject of the current Solution is the elimination of the fasting condition requirement as well as potential sourcing for a more efficient oral delivery technology that can be applied to GLP-1 agonist and GLP-1/GIP co-agonist compounds in man.