Rani Therapeutics has revealed new pharmacokinetic (PK) and pharmacodynamic (PD) data from a preclinical study evaluating the oral delivery of the glucagon-like peptide-1 receptor (GLP-1) agonist semaglutide administered via the RaniPill capsule.
Rani has developed the RaniPill capsule, which is a novel, proprietary and patented platform technology, intended to replace subcutaneous (SC) injection or intravenous infusion of biologics and drugs with oral dosing. Currently, semaglutide is only available as a SC injection for the treatment of obesity and is marketed in the US by Novo Nordisk as Wegovy. The RaniPill capsule moves through the stomach – where acids typically break down drugs – intact and then reaches the intestine where it delivers the drug into the intestinal wall. The highly vascularised intestinal wall allows the drug to be absorbed rapidly.
“The target product profile of semaglutide in the RaniPill capsule would be once-weekly oral administration of semaglutide therapy, which we believe may be more convenient for patients and could lead to improved adherence,” explained Talat Imran, Chief Executive Officer of Rani Therapeutics. “Overall, the totality of the preclinical data we have generated in the obesity space demonstrating the successful delivery of both single and triagonist incretin therapies gives us confidence to continue building our obesity portfolio to unlock the true value of the RaniPill technology. Looking ahead, we are excited to begin our Phase 1 study for RT-114, Rani’s GLP-1/GLP-2 dual agonist in partnership with ProGen this year.”
The nonclinical PK and PD study was conducted to examine the effects of semaglutide delivered orally via the RaniPill (RT-116) versus a SC injection comparator group. The 2x2 crossover study was conducted in two parts with a period of 4 weeks separating the two groups to evaluate the PK, PD and safety of RT-116.
Eight canines were randomised into two groups who received 0.5mg of semaglutide delivered via oral administration of the RaniPill HC (n=4) or SC injection (n=4). Endpoints included plasma drug concentrations, body weight, food intake, lipid profile and safety.
Key findings:
Semaglutide was successfully delivered in 7 of 8 canines that received the RaniPill capsule.
Semaglutide administered via the RaniPill capsule was well tolerated with no serious adverse events.
Oral administration via the RaniPill capsule demonstrated bioavailability and biological activity comparable to subcutaneous administration.
The relative bioavailability of oral semaglutide was 107% versus subcutaneous administration.
Both groups saw comparable weight loss which appeared to be driven by decreased food intake that coincided with rises in plasma drug levels thus indicating there is a PD effect to treatment.
Both groups saw comparable moderate decreases in serum triglycerides and cholesterol.
“There are currently no approved orally-administered GLP-1 agonists on the market for the treatment of obesity,” said Jesper Høiland, Senior Strategic Advisor for Rani Therapeutics and former executive at Novo Nordisk. “While Rybelsus is an oral version of semaglutide approved to improve glycaemic control in adults with type 2 diabetes mellitus, it requires daily administration at a significantly higher dose than the subcutaneous equivalent. In comparison, the RaniPill HC harnesses advanced technology to deliver the same dose as the subcutaneous injection of semaglutide with expected weekly oral administration. I believe that a convenient, once-weekly oral version of semaglutide delivered via the RaniPill HC has the potential to be transformational as a next generation treatment that would impact how obesity is treated worldwide.”
Initiation of Phase 1 clinical trial of RT-114 containing a GLP-1/GLP-2 dual agonist for the treatment of obesity is expected in 2025.
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