Valbiotis Announces the Positive Results of Its Clinical Study on the Bioavailability and Mode of Action of TOTUM•070, Against Hypercholesterolemia
29 Mar 2022
LipidriveHypercholesterolemia
Valbiotis (FR0013254851 - ALVAL, PEA-SME eligible), a Research and Development company committed to scientific innovation for preventing and combating metabolic and cardiovascular diseases, announces the positive results of its clinical study on the bioavailability and mode of action of TOTUM•070 against hypercholesterolemia.
This innovative protocol, involving 10 healthy volunteers, has first confirmed the presence of 22 metabolites2 of interest in the serum3 of volunteers. The analyses were conducted following oral administration of the clinical dose of 5g of TOTUM•070, used also in the Phase II HEART study. Most of the 22 metabolites are already known for their activity on metabolism. Mode of action analyses then demonstrated, among other things, two effects of TOTUM•070 on human liver cells: inhibition of the cholesterol synthesis pathway and inhibition of cholesterol storage in hepatocytes. These two effects on cholesterol in the liver, which is one of the main metabolic organs, speak in favor of TOTUM•070’s potential against hypercholesterolemia. Following on from these positive results, Valbiotis will announce the outcome of its Phase II HEART clinical efficacy study in the second quarter of 2022, as planned. Its primary endpoint is the reduction of blood LDL-cholesterol.
Pascal SIRVENT, Director of Discovery and Preclinical and Translational Research and Member of the Board of Directors, states: “For the first time, this clinical study has evaluated the bioavailability and hepatic mode of action of TOTUM•070 in humans. The results live up to our expectations: we can confirm that TOTUM•070 contains many metabolites of interest for regulating cholesterol. Most importantly, the results show that these metabolites are bioavailable in humans and have two significant effects on the regulation of cholesterol in the cells of the human liver, one of the main metabolic organs. These novel clinical data build on the positive preclinical results presented in 2021 and pave the way for further mode-of-action investigations in the liver. Above all, they confirm the potential of TOTUM•070 against hypercholesterolemia in humans, pending the imminent results of our Phase II clinical efficacy study.”
Murielle CAZAUBIEL, Director of Medical, Regulatory and Industrial Affairs and Member of the Board of Directors, adds: “During this clinical study on TOTUM•070, we used an innovative methodology adapted to our plant-based active substances that combines metabolomics and mode of action, which is now producing results. This is a positive clinical development and a very encouraging sign while we wait for the Phase II HEART clinical efficacy results, which will become available in the second quarter of 2022.”
Results of the clinical study on bioavailability and mode of action
This study was conducted on 10 healthy volunteers in an open-label setting and followed a protocol combining metabolomics and mode of action, designed and implemented by Clinic’n’Cell. Professor Gisèle PICKERING, coordinator of the Clinical Investigation Center of the Clermont-Ferrand University Hospital, was Principal Investigator4.
Metabolomic analysis consists of characterizing the metabolites of an active substance in serum, i.e., the molecules derived from this active substance following their intestinal absorption and passage into the blood. After a single oral dose of 5g of TOTUM•070, which is the clinical daily dose, used also in the HEART clinical study (see below), analysis of the volunteers’ serum confirmed the presence of 22 metabolites of interest, the majority of which are known to have a biological activity on metabolism. Kinetic measurements validated good bioavailability of these metabolites in serum within three hours of oral TOTUM•070 intake.
In a second step, the serum collected from volunteers after oral intake of 5g of TOTUM•070 – a serum rich in active metabolites from TOTUM•070 – was used to conduct in vitro tests on human liver cells exposed to massive lipid intake. In this context of “lipotoxic stress”, the volunteers’ serum exerted two major effects on these human liver cell lines: inhibition of the de novo cholesterol synthesis pathway1 and inhibition of cholesterol storage. It also showed no toxicity.
All analyses were conducted with a double control: cell cultures with and without lipotoxic stress, then with and without serum enriched in active metabolites.
Upcoming publication of the Phase II clinical results of TOTUM•070 on hypercholesterolemia
The Phase II HEART clinical trial results will be announced in the second quarter of 2022. This multi-center study will evaluate the efficacy of TOTUM•070 in reducing blood LDL-cholesterol levels versus placebo, in 120 volunteers with mild to moderate untreated hypercholesterolemia. These results will be decisive for the marketing of TOTUM•070, an innovative 100% plant-based active substance containing neither phytosterols nor red yeast rice, and for its positioning as a reference non-drug option against LDL-cholesterol.
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