MetP Pharma AG, leveraging the proprietary nose-to-brain drug delivery technology BrainDos in internal and external product development and manufacturing programs, recently announced its preclinical research results. According to the company’s statement, the results support the further development of semaglutide in an oleogel formulation using the BrainDos drug delivery technology.
Semaglutide, the active ingredient of Ozempic and Wegovy, is an antidiabetic medication used for the treatment of type 2 diabetes as well as an anti-obesity medication used for long-term weight management. It is a Glucagon-Like Peptide-1 Receptor Agonist (GLP-1-RA) that is currently administered through subcutaneous injection using pens.
GLP-1 receptors are found on beta cells of the pancreas and on neurons of the brain. There, signal chains are activated that suppress the feeling of hunger and increase the feeling of satiety. It is proven that GLP-1 RAs can send information to the brain via neural and humoral pathways.
Preclinical studies in Cultured Human Airway Epithelial Cells (Calu-3) conducted at MetP Pharma AG demonstrate that the semaglutide oleogel in the BrainDos formulation leads to a ten-fold increase in tyrosine hydroxylase (TH) expression, compared to only a two-fold increase of the aqueous semaglutide solution as used for example in pens.
As obesity leads to a reduction in tyrosine hydroxylase (TH) levels (1) an increase in TH levels is a suitable biomarker for drug delivery. The results also demonstrate a significantly higher TH response at four hours than at 24 hour post treatment but the TH level at 24 hour is still about three-fold higher than the untreated control demonstrating consistent activity. The semaglutide concentration in both the oleogel formulation and the aqueous solution was 10nM.
Dr. Claudia Mattern, Chief Scientific Officer at MetP Pharma says, “The preclinical studies clearly show that the oleogel formulation with BrainDos increases the delivery of semaglutide into cells. This makes BrainDos™ suitable for re-formulating active ingredients with expiring patents and re-patenting them using a new, innovative application method. It is important to understand that BrainDos™ is an innovative nose-to-brain drug delivery technology that in no way is comparable to traditional nasal sprays.”
A nasal application of semaglutide could have several advantages compared to pens such as non-invasiveness, fast and easy administration, painless application for patients with needle phobia, fewer adverse events through reduced systemic exposure of the drug, and much less costs per application than pens. In addition, there is the ability for direct CNS delivery using BrainDos potentially resulting in a higher bioavailability.
This new formulation and administration mode could help alleviate the obesity-related healthcare problem as the manufacturing costs are significantly lower than with the currently used pens and the application is more convenient.
Semaglutide in the BrainDos formulation (green) leads to a highly significant increase in tyrosine hydroxylase (TH) expression, compared to the aqueous semaglutide solution as used for example in pens (red).