The pharmaceutical landscape for metabolic health is witnessing a tectonic shift. While injectable GLP-1 receptor agonists (GLP-1RAs) have set new standards for weight loss and glycemic control, the “holy grail” of metabolic medicine remains the reliable, needle-free delivery of multi-hormonal peptides. A significant breakthrough in this space has arrived via a novel pharmaceutical composition (documented in patent US12544349B1) that pairs the potent GLP-1/glucagon dual agonist pemvidutide with a specialized class of permeation enhancers.
The Bioavailability Hurdle
Peptides like pemvidutide are notoriously fragile; when taken orally, they are typically destroyed by the acidic environment of the stomach and the aggressive enzymes of the gastrointestinal tract. To achieve systemic circulation, these drugs must survive proteolysis and traverse the intestinal membrane.
Historically, oral GLP-1 formulations (such as Rybelsus®) have relied on massive doses to overcome a bioavailability of less than 1%. Furthermore, patients face strict dosing protocols-such as fasting for at least 30 minutes post-dose-to ensure any absorption occurs at all.
The Technology: AC-aa-NS and NaGly(N-Bn)C8
The breakthrough described in the recent patent centers on a unique class of enhancers called acylated amino acids substituted on the amine function (AC-aa-NS). Specifically, the formulation utilizes NaGly(N-Bn)C8, a compound that performs two critical functions simultaneously:
- Permeation Enhancement: It facilitates the passage of the large pemvidutide molecule across the intestinal wall.
- Unexpected Protease Inhibition: In a “surprising” discovery, the applicant found that these acylated amino acids also act as protease inhibitors, protecting pemvidutide from enzymatic degradation.
Clinical Evidence: Results from Beagle Dog Studies
To validate this breakthrough, independent pharmacokinetic (PK) studies were conducted in Beagle dogs. The results demonstrated that this specific formulation (Composition A.1.1) successfully delivered pemvidutide orally with remarkable consistency:
- Total Exposure: Pemvidutide exposure was detected in 100% of the test subjects across two independent studies.
- Consistency: The studies reported a median AUClast of $225~h*ng/mL$ and $246~h*ng/mL$, respectively, indicating low inter-study variability.
Why Pemvidutide?
The choice of pemvidutide as the active payload is strategic. As a 1:1 GLP-1/glucagon dual agonist, it offers a “diet and exercise in a pill” effect. While the GLP-1 component suppresses appetite, the glucagon component increases energy expenditure and directly targets liver fat metabolism.
This dual-action approach is critical for treating Metabolic Dysfunction-Associated Steatohepatitis (MASH)-a condition for which pemvidutide recently received FDA Breakthrough Therapy Designation. Clinical trials have shown that pemvidutide can achieve up to 59.1% MASH resolution without worsening fibrosis while preserving lean muscle mass significantly better than traditional GLP-1 monotherapies.
Conclusion
By overcoming the “bioavailability gap” through dual-function AC-aa-NS enhancers, this new patent marks a turning point in metabolic therapy. Transitioning a breakthrough molecule like pemvidutide from a weekly injection to a daily pill could drastically increase patient compliance and open the door to treating millions of patients earlier in their disease progression.
Interested in how AC-aa-NS technology enables oral delivery of pemvidutide and overcomes the GLP-1 bioavailability barrier? Fill out the form to receive a customized patent insight.
