TOTUM•070: dyslipidemia

TOTUM•070 is a unique patented combination of plant extracts, clinically proven for patients with untreated, mild to moderate LDL hypercholesterolemia, associated with a moderate overall cardiovascular risk.

Overview

Hypercholesterolemia: a major, yet modifiable, cardiovascular risk factor

Over time, excess blood cholesterol, in particular LDL cholesterol, weakens and narrows the arteries. This “atherosclerosis” contributes to the onset of serious diseases such as heart attack, stroke and arteritis of the lower limbs.
Hypercholesterolemia affects 39% of adults worldwide according to the WHO, 48% in North America, 54% in Europe and 62% in France. Treatment is based on lifestyle changes, combined with prescribed drugs for patients with a high risk of cardiovascular disease. For patients classified as medium-risk, there are few non-drug, clinically proven preventive treatment options available.

Sources:
– De Peretti C et al., Étude nationale nutrition santé (ENNS) 2006-2007;
– Benjamin EJ et al., American Heart Association. Circulation. 2017;
– US Preventive Services Task Force, Final Recommendation Statement, JAMA, 2016.
¹www.inserm.fr/information-en-sante/dossiers-information/atherosclerose 

Key Figures

1.6 g/l: this is the normal level of blood LDL cholesterol for patients with no additional cardiovascular risk factor. Above this level, LDL hypercholesterolemia is diagnosed and the risk of cardiovascular disease increases.

Source: Fédération française de cardiologie, 2021, https://www.fedecardio.org/je-m-informe/le-cholesterol/ (accessed June 29, 2022).

A 10% reduction in the blood LDL cholesterol levels of hypercholesterolemic patients reduces the risk of heart disease by 50% over five years.

Source: WHO, Global Health Observatory (GHO, data on men aged > 40 years old).

Active substance

TOTUM•070 is a combination of plant extracts, with no phytosterol or red yeast rice content, for which a patent has been filed in 24 countries and has already been granted in Europe and the USA.

This exclusive active substance has been developed in particular for patients with mild to moderate LDL hypercholesterolemia of up to 190 mg/dl, untreated and associated with an overall moderate cardiovascular risk.

TOTUM•070 is being developed with a view to obtaining a proprietary health claim relating to the reduction of blood LDL cholesterol, a risk factor for cardiovascular diseases.

Illustrative purpose only – product not marketed
See the mode of action

Preclinical results

Led on two different in vivo models, predictive of human pathophysiology, the studies showed that TOTUM•070 prevents hypercholesterolemia. Initial mode of action data also reveal significant effects on several key mechanisms for the regulation of lipid metabolism, notably intestinal, hepatic and inflammatory.

These preclinical data were presented in November 2021 at the annual congress of the American Heart Association (AHA).

Models of hypercholesterolemia induced by a high-fat diet (HFD)

In these models, data demonstrate a profound efficacy of TOTUM•070 on circulating lipids, with a dose-dependent reduction compared to the high-fat diet alone:

  • 37 to 48% reduction of “bad” cholesterol (non-HDL, including LDL);
  • 31 to 42% of total cholesterol;
  • 30 to 46% of blood triglycerides.

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A multi-target mode of action

Clinical and preclinical studies have documented the multi-target mode of action of TOTUM•070. According to these data, the lipid-lowering effect of TOTUM•070 is mainly based:

  • at the intestinal level, on the reduction of the absorption of cholesterol;
  • at the hepatic level, on the reduction of de novo cholesterol synthesis.

In these studies, additional liver benefits were observed, with a decrease in cholesterol storage and a decrease in gene expression of inflammatory markers.

Clinical development

The results of the Phase II HEART clinical study were published on June 13, 2022.

This multicentric, international, randomized, placebo-controlled, double-blind study involved 120 people with untreated mild to moderate hypercholesterolemia, with blood level of LDL cholesterol between 130 mg/dl and 190 mg/dl. The participants were divided into two equivalent arms of 60 people, supplemented for six months with a daily dose of 5 g of TOTUM•070 or a placebo, in two intakes.

After a 6-month supplementation, the study achieved its objective of significantly reducing LDL cholesterol in the blood (primary endpoint, -9% versus placebo, p<0,01). As early as 3 months of supplementation with TOTUM•070, the results showed a significant lipid-lowering effect, with:

  • a significant 13% reduction in blood LDL cholesterol level, compared to placebo (p<0.01);
  • a significant 14% reduction in blood triglyceride level, compared to placebo (p<0.05).

In clinical practice, the reduction of LDL blood cholesterol as early as 3 months of supplementation is an expected benefit by patients and healthcare professionals. The HEART study also demonstrates the persistent lipid-lowering effect at 6 months.

In addition, the study confirmed the safety and very good tolerance of TOTUM•070.

The comprehensive data from the study will be presented at international scientific conferences.

Previously, an open label bioavailability and mode of action study was led on 10 volunteers. Published in March, 2022, the positive results validated the bioavailability of TOTUM•070 metabolites and their effects on human liver cells in vitro.

Intellectual property

The patent has been granted in key markets : USA, Europe, Japan, Mexico, South Africa, Brazil.

 

 

 

 

Funding

The European Union participated in the financing of the research project on TOTUM•070.
https://www.europe-en-nouvelle-aquitaine.eu/fr