Poxel SA is a biopharmaceutical company headquartered in Lyon, France, dedicated to developing innovative treatments for metabolic diseases including type 2 diabetes and non-alcoholic steatohepatitis (NASH). Recently, the company announced the results of two clinical studies of the new oral hypoglycemic agent imeglimin. These 2 studies evaluated the possibility of imeglimin interacting with two widely prescribed hypoglycemic agents, metformin (metformin) and sitagliptin (sitagliptin, DPP-4 inhibitor). The results showed that in healthy subjects, imeglimin and metformin or sitagliptin co-administered without causing clinically relevant pharmacokinetic interactions. The results of the two studies have been published online in the life sciences journal "Clinical Pharmacokinetics". The article title is: Imeglimin Does Not Induce Clinically Relevant Pharmacokinetic Interactions When Combined with Either Metformin or Sitagliptin in Healthy Subjects.
The main purpose of the two drug interaction studies was to evaluate the effect of repeated coadministration of metformin or sitagliptin with imeglimin on the pharmacokinetic parameters of metformin or sitagliptin in healthy subjects. The secondary goals of the two studies were safety and tolerability. The results of both clinical studies indicate that imeglimin is safe and well tolerated, and there are no clinically relevant changes in the level of systemic drug exposure.
David E. Moller, MD, Poxel ’s Chief Scientific Officer, said: “Type 2 diabetes is a progressive disease that requires additional treatment medications over time. For patients with type 2 diabetes who receive a treatment whose blood sugar is no longer controlled, Successful management usually progresses to combination therapy with drugs with complementary mechanisms of action. The safety and tolerability curves of imeglimin combined with metformin or sitagliptin observed in these studies and several other evaluations Studies on the use of different drugs are consistent, including the key phase III TIMES 2 trial and two previous phase II trials, which also showed the potential to increase efficacy. These results highlight imeglimin as an innovative new treatment regimen to supplement existing anti-cancer drugs The potential for diabetes treatment. "
Dr. Sebastien Bolze, chief operating officer and executive vice president of Poxel's nonclinical and manufacturing operations, said: "imeglimin is the first drug candidate of a new oral drug targeting the mitochondrial respiratory chain, which is where the cells produce energy. These results indicate , Imeglimin will not cause clinically relevant changes in the pharmacokinetic curves of two important drugs in the diabetes treatment ammunition library. These results are consistent with previous preclinical and long-term clinical studies. "
The molecular structure of imeglimin (Source: Wikipedia)
imeglimin belongs to a new class of oral chemical preparations called Glimins. It is the first candidate product of this class to enter clinical development. It has a unique mechanism of action (MOA) and targets mitochondrial bioenergetics. It is the only oral hypoglycemic agent that can simultaneously act on all three key organs (liver, muscle, pancreas) involved in glucose homeostasis.
imeglimin has been shown to reduce blood sugar by increasing insulin secretion, increasing insulin sensitivity, and inhibiting gluconeogenesis. This mechanism of action has the potential to prevent endothelial dysfunction and diastolic dysfunction, and has a protective effect on microvascular and macrovascular defects caused by diabetes. In addition, imeglimin also has potential protective effects on the survival and function of β cells. This unique mechanism of action provides imeglimin with unlimited potential to treat type 2 diabetes in almost all stages of the current hypoglycemic treatment model, including as a monotherapy or as an additional therapy for other hypoglycemic agents.
The imeglimin mechanism is unique and has the potential to help manage type 2 diabetes at all stages of the disease
Poxel and Sumitomo Pharmaceutical established a strategic partnership in October 2017 to develop and commercialize imeglimin for the treatment of type 2 diabetes in Japan, China, South Korea, and nine other countries in Southeast Asia and East Asia. At the end of last year, the phase III clinical development project of imeglimin for the treatment of type 2 diabetes was successfully completed. The project evaluated the efficacy and safety of imeglimin in the treatment of Japanese patients with type 2 diabetes to support the safety and effectiveness of imeglimin in different patient groups. The project includes three key phase III studies involving more than 1,100 patients. In these studies, imeglimin was administered at a dose of 1000 mg twice daily.
The results of the TIMES project confirmed the differentiated characteristics of imeglimin, showing that imeglimin has a dual mechanism of action to increase insulin secretion and improve insulin sensitivity, and it shows an increased hypoglycemic effect when combined with drugs with complementary mechanisms of action, including DPP-4 inhibition Agents, SGLT2 inhibitors, biguanides, sulfonylurea drugs, gleneides, alpha-glucosidase inhibitors, thiazolidine drugs, GLP1 receptor agonists. Based on the project data, Poxel and Sumitomo Pharmaceuticals are preparing for the submission of imeglimin's new drug application (NDA) in Japan, which is expected to be submitted in the third quarter of 2020 and will bring the product to the Japanese market in 2021.
In February 2018, Roivant Sciences and Poxel signed a $ 650 million agreement to develop and commercialize imeglimin in markets outside the aforementioned countries and regions, including the United States and the European Union. Currently, Poxel is working with Metavant, a subsidiary of Roivant Sciences, to advance imeglimin into a phase III project.
imeglimin has a unique and differentiated mechanism and good safety and tolerability. The drug has the potential to become an important new treatment option to help patients manage type 2 diabetes at multiple stages of the disease.（Bioon.com）