12 July 2019 - - Switzerland-based clinical-stage biopharmaceutical company Metavant Sciences and France-based Poxel SA (Euronext: POXEL FR0012432516) have received positive topline results from a PK/PD clinical trial for imeglimin, an investigational oral therapy for the treatment of type 2 diabetes, the company said.
The Metavant study evaluated the safety, tolerability and PK/PD of imeglimin in individuals with type 2 diabetes and chronic kidney disease stages 3b/4.
Imeglimin met the primary objective of being well-tolerated in this specific patient population, confirming the safety profile observed to date and demonstrating its potential in this patient population. This completes one of the key activities to prepare for a Phase 3 programme in the US and Europe.
The primary objective of the 28-day, randomized, placebo-controlled, parallel design study in individuals with type 2 diabetes and CKD stages 3b/4 was to evaluate the safety, tolerability and pharmacokinetics of imeglimin. Exploratory objectives included measures of glycemic control.
A total of 49 subjects with HbA1c levels ranging from 6.0% to 12.0% were assigned to one of four treatment groups (500 mg twice a day, 1500 mg once a day, 1000 mg twice a day, or placebo) for 28 days.
There were no serious adverse events reported and no cases of lactic acidosis were observed. All treatment-related adverse events were mild or moderate, with the most common being diarrhea (18.2% in placebo group, 10.5% in the total imeglimin treated group).
Imeglimin PK was as predicted from modeling previously performed by Poxel. Data from this study will inform dosing for the Phase 3 program in subjects with type 2 diabetes and CKD stages 3b/4.
Multiple measures of glycemic control in this new population with type 2 diabetes were consistent with previous Poxel data.
On February 12, 2018, Roivant Sciences and Poxel announced a strategic development and license agreement for imeglimin in the US, Europe and all other countries not covered by Poxel's existing agreement with Sumitomo Dainippon Pharma in East and Southeast Asia.
Imeglimin is the first clinical candidate in a new chemical class of agents called glimins. Imeglimin acts on the three key organs which play an important role in the current anti-diabetic treatment paradigm: the liver, muscles, and the pancreas.
In several studies conducted to-date, imeglimin has demonstrated potential glucose-lowering effects through increased insulin secretion in response to glucose, increased insulin sensitivity, and suppression of gluconeogenesis.
Imeglimin's mechanism of action also has the potential to provide protective effects on endothelial and beta cell survival and function. Imeglimin has been evaluated in a total of 28 clinical trials in over 2,500 subjects with type 2 diabetes in the US, Europe, and Japan.
The trials have consistently met their primary objective, which demonstrated improved glycemic control in patients with type 2 diabetes with a favorable side effect profile observed.
Poxel uses its development expertise in metabolism to advance a pipeline of drug candidates focused on the treatment of metabolic disorders, including type 2 diabetes and non-alcoholic steatohepatitis.
We have successfully completed the Phase 2 clinical program for our first-in-class lead product, Imeglimin, which targets mitochondrial dysfunction, in the US, Europe and Japan.
Together, with our partner Sumitomo Dainippon Pharma, we are conducting the Phase 3 Trials of Imeglimin for Efficacy and Safety (TIMES) program for the treatment of type 2 diabetes in Japan.
Our partner Roivant Sciences is responsible for Imeglimin's development and commercialization in countries outside of Poxel's partnership with Sumitomo Dainippon Pharma, including the US and Europe.
PXL770, a first in class direct adenosine monophosphate-activated protein kinase activator, is in a Phase 2a proof-of-concept program for the treatment of NASH. PXL770 could also have the potential to treat additional metabolic diseases.
PXL065 (deuterium-stabilized R-pioglitazone), a mitochondrial pyruvate carrier inhibitor, is in Phase 1 and being developed for the treatment of NASH.
Poxel also has additional earlier-stage programmes, including deuterated drug candidates for metabolic, specialty and rare diseases.
Metavant Sciences, a member of the Roivant family of companies, is a clinical-stage biopharmaceutical company committed to developing innovative therapies for metabolic disorders.
Roivant Pharma is the biopharmaceutical business unit of Roivant Sciences. Roivant Pharma is focused on end-to-end biopharmaceutical company creation, launch, and oversight. Roivant Pharma companies include Altavant, Aruvant, Axovant, Dermavant, Enzyvant, Genevant, Immunovant, Metavant, Myovant, Respivant, Urovant, and Arbutus.
Roivant aims to improve health by rapidly delivering innovative medicines and technologies to patients. Roivant does this by building Vants nimble, entrepreneurial biotech and healthcare technology companies with a unique approach to sourcing talent, aligning incentives, and deploying technology to drive greater efficiency in R and D and commercialisation.