This graphical representation displays the ileum interior covered by intestinal villi. The enteroendocrine cells are shown in light blue colour. The 7TM receptors on the microvili are stimulated by fat and carbohydrate metabolites (displayed as yellow spheres and white cubes). Upon stimulation the enteroendocrine cell releases hormones to the blood vessel, i.e. ileal brake signalling.
The worldwide burden to obesity is estimated to 1.5 billion overweight and 500 million obese individuals, defined as a body mass index (BMI) of 30 kg/m2 or greater. In USA and in countries across Europe 30-70% of the population are overweight, with a BMI of 25-29.9 kg/m2. Overweight and obesity is the fifth leading risk for global deaths. Among the most troubling obesity-related trends has been the almost 50% increase of overweight children and adolescents in the last decades of the 20th century.
Despite this clearly identified serious health issues directly related to obesity on a global scale, there is not yet a sufficient tool-box of treatments available for physicians to reverse the obesity trends. The treatment alternatives for overweight and obese patients are obviously not fully successful when considering both efficacy and safety. Firstly, life style changes have low compliance and consequently poor long-term effects. Secondly, available oral medications have a limited efficacy (5-10% weight loss) and often associated with troublesome side-effects. Thirdly, bariatric surgery, is effective but irreversible, and may result in multiple severe adverse effects.
Empros Pharma address this unmet and strong medical need for a safe and effective medical product by developing EMP16, a novel oral and locally active medical treatment for overweight and obesity and related common metabolic disorders such as type-2 diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD is one of the causes of fatty liver, occurring when fat is deposited (steatosis) in the liver due to causes other than excessive alcohol use. NAFLD is the most common liver disorder in developed countries. NAFLD is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states (e.g. type-2 diabetes) and weight management. If not treated NAFLD may progress into liver cancer. Another common disease is polycystic ovary syndrome (PCOS) that might be successfully treated with EMP16 in the future. EMP16 entered clinical phase IIa during 2016 and the results will be reported during 2017. The objective is to develop a safe, highly tolerable oral local treatment that reduces body weight more than established therapy (>8-12%).
The main mechanism of action for EMP16 is to delay the normal food digestion and absorption processes to the end of the small intestine (see the graphical representation on top of this page). The main mechanism is local enzyme inhibition of various amylases and lipases responsible for carbohydrate and lipid digestion in the gastrointestinal tract. The gastrointestinal tract is an organ for enzyme mediated digestion and absorption of ingested food as well as it is largest endocrine (hormone secretion) organ in the body. Satiety is triggered by a complex interplay between hormones, nutrients and transmitter substances in the body. Digested food reaching the end of small intestine leads to an increased secretion of several gut hormones that act locally through receptor in specialized enteroendocrine cells on the motility of the gastrointestinal tract and on the brain centre regulating satiety. The gastric motility is regulated so that stomach emptying rate and food transit rate through the upper part of the gastrointestinal system slows down. This effect is commonly known as the ileal brake and is mediated by locally released gut hormones when digestion and absorption of free fatty acids and hexoses (i.e. glucose) act via specialized receptors in ileum. The shift on gastrointestinal digestion induced by EMP16 is expected to increase satiety by increasing the local hormone response, once the digested carbohydrates and lipids are absorbed by the intestinal enteroendocrine cells where these specific receptors are located. EMP16 acts locally in the gastrointestinal system through re-routing digestion and the exposure of natural dietary derived ligands (i.e. digested carbohydrates and lipids) to important satiety and eating behaviour regulating mechanisms.
EMP16 is based on a proprietary advanced drug delivery technology, designed to have features that optimizes its effect throughout the gastrointestinal tract. EMP16 is an oral product with a local effect in the gastrointestinal systems. It is a fixed dose combination of two locally active, safe and established active drugs. EMP16 is a multiple unit, modified release formulation designed to target the satiety regulation via the ileal brake mechanism. The advanced multiple unit, modified release formulation is designed to maximize the effect of the drugs as well as improving tolerability. The mechanism of action of EMP16 is based on supporting and increasing the natural satiety response present in the gastrointestinal systems to regulate food intake.
Distinct to other hormone based satiety regulating pharmaceuticals that act on one or a few of the hormone signalling pathways, EMP16 enhances the entire endogenous hormone response in a physiological way. Empros Pharma expects that this is a safer and more potent method to address the unmet medical need of obese patients. The design of an advanced multiple unit and function oral dosage form is also expected to significantly reduce local side-effects and to increase tolerability.