Elafibranor(GFT505) Powder–The New Drug For NASH Treatment Study
What is Elafibranor (GFT505)?
Elafibranor (GFT505) powder (923978-27-2), is an experimental drug whose research is still underway. Mainly, its study and development by Genfit are based on the effectiveness of Elafibranor (GFT505) powder (923978-27-2) in fighting diseases like non-alcoholic fatty liver disease, dyslipidemia, insulin resistance, and diabetes.
Elafibranor (GFT505) mechanism of action
Elafibranor (GFT505) powder is an oral treatment that works on the three PPAR subtypes. They include PPARa, PPARd, and PPARg. However, it mainly acts on PPARa.
The Elafibranor mechanism of action is complicated as it differentially recruits cofactors to the nuclear receptor. As a result, this leads to the differential regulation of genes as well as the biological effect.
Elafibranor(GFT505) powder is capable of identifying and profiling the selective nuclear receptor modulator (SNuRMs) activity. As a result, it offers improved efficiency with reduced side effects.
Both the multimodal and pluripotent molecules have proven to be effective in fighting various conditions. They include insulin resistance and diabetes, inflammation, obesity, and lipid triad, which is characterized by an increase in the HDL cholesterol and lowering of the LDL cholesterol and triglycerides.
The difference between the Elafibranor’s mechanism of action and that of other compounds that target PPARs in NASH (nonalcoholic steatohepatitis) is the fact that it does not exhibit any pharmacological PPARy activity.
As a result, Elafibranor users do not experience unwanted side effects that are associated with PPARy activation. Such side effects include; fluid retention, edema, and weight gain all which increase one’s risk in suffering from heart failure.
Elafibranor (GFT505) for Nash treatment study
NASH (nonalcoholic steatohepatitis) is a liver disease which leads to the inflammation and degeneration of the hepatocytes as well as accumulation of fat which are also known as lipid droplets. Usually, certain health conditions like metabolic syndrome, type 2 diabetes, and obesity are the number one cause of nonalcoholic steatohepatitis (NASH), and nonalcoholic fatty liver disease (NAFLD).
Today, many people are suffering from this deadly disease. The scary part about it is that it could lead to cirrhosis, a condition which makes the liver unable to function. It could also progress to liver cancer and in some cases, cause death.
The sad news about NASH (nonalcoholic steatohepatitis) is that it does not pick on the age and continues to affect everyone. Worse still, the disease signs could be asymptomatic, and one may never know that they are suffering from the disease until it has advanced to a later stage.
The scarring and inflammation brought about by NASH (nonalcoholic steatohepatitis) could also lead to cardiac and lung complications. With many people now suffering from this condition that originates from nonalcoholic fatty liver disease, researchers are looking for treatment options other than a liver transplant.
One of the drugs being studied for NASH treatment is Elafibranor(GFT505) powder(923978-27-2). So far, it has shown to cause positive effects on the two main characteristics of the disease, i.e., ballooning and inflammation. The beauty with it is that it is highly tolerable and will rarely make one suffer from any side effects. It is for this reason that the U.S Food and Drug Administration has given a fast-track designation to this drug for NASH treatment.
Currently, Elafibranor (GFT505) powder is in Phase 3 clinical trial, also dubbed as RESOLVE IT.
It is a global study that began in the first quarter of 2016, which is randomized, placebo-controlled in ratio 2:1 and double-blind. Patients who are involved in this study are those who suffer from NASH (NAS>=4) and fibrosis (F2 or F3 stages whereby the liver damage is already notable. Throughout the study, the patients will either be administered with Elafibranor(GFT505) dosage 120mg or placebo once every day.
The first one thousand patients to be enrolled will help show if NASH is treatable with Elafibranor (GFT505) without worsening fibrosis as compared to those treated with placebo.
The first cohort was enrolled in April 2018, and the analysis of the results will be reported in late 2019. The data reported will determine whether Elafibranor gets approved by the U.S Food and Drug Administration as gets a conditional approval by the European Medicines Agency, well known as EMA by 2020.
The study went a step forward in December 2018 when the Data Safety Monitoring Board (DSMB) endorsed the continuation of the trial without any alteration. That was after a pre-planned review on the safety data done after thirty months.
Results for the prior preclinic and clinical studies in the treatment for NASH
The efficacy and safety ofElafibranor in NASH treatment have been evaluated in the past through multiple disease models. In the 5 phase 2a, various trials were done on different populations of patients suffering from metabolic disease. It included those with type 2 diabetes or pre-diabetes and atherogenic dyslipidemia. During the study, it was observed that Elafibranor promoted;
- Reduced risk of suffering from cardiovascular issues
- Reduced markers of liver injury
- Anti-inflammatory properties
- Increased insulin sensitivity
- Glucose homeostasis
- Cardioprotective lipid profile.
The phase 2b trial that was launched in 2012 was the biggest interventional trial and the first real international study to be done on NASH. It is then that Elafibranor attained the FDA recommended endpoint of “NASH Resolution without the worsening of Fibrosis.“That was the primary endpoint for the global phase 3 trial that is still ongoing.
It was observed that patients who got NASH treatment with Elafibranor noted an improvement in the liver dysfunction markers such as ALP, GGT, and ALT. Through the evaluation of the secondary endpoints, there was an observation that Elafibranor (GFT505) dosage 120mg gave therapeutic effects on the cardiometabolic risk factors associated with NASH, They included;
- Anti-inflammatory effects
- An improvement in insulin sensitivity and glucose metabolism in patients who have diabetes
- Improve the levels of lipoproteins and plasma lipids.
The effectiveness of Elafibranor in the treatment of pediatric NASH
The rate at which children are suffering from obesity has increased significantly, making it a growing health concern. In a study done in 2016, it was observed that NAFLD(nonalcoholic fatty liver disease) affects about 10-20% of the pediatric population. It further showed that pediatric NAFLD would be the leading cause of liver failure, liver pathology, as well as liver implantation in children and adolescents.
In January 2018 there was the official launching of NASH pediatric program having in mind that Elafibranor is the only drug that has proven to be effective in NASH treatment in adults and is in the development stage in the treatment of children.
Can Elafibranor be used together with other drugs in NASH treatment?
It is already clear that Elafibranor is effective in NASH treatment when used on its own. However, due to the complexity of the sickness, it could be used together with other drugs in the management of liver fibrosis, NASH, and their co-morbidities.
Elafibranor (GFT505) other uses
In cholstasis disease treatment
Cholestasis is a condition caused by the impairment in the formation of bile and its flow through the gallbladder and duodenum. It could lead to the worsening of systemic disease and liver disease, liver failure, and even the need for liver transplantation. A clinical study done showed that Elafibranor (GFT505) powder reduces the biochemical markers in the plasma hence proving that it can be useful in the treatment of cholestasis disease.
Diabetes is a condition that is caused by having too much sugar or glucose in the blood. It affects around four hundred million people globally. One develops type 2 diabetes once their body is not able to produce and use insulin normally.
Research done on elafibranor shows that it reduces the progression of type 2 diabetes in two ways. The first one is through the improvement of glucose metabolism in the body.
It also improves insulin sensitivity in the muscles and peripheral tissues.
The Elafibranor study comes as good news to anyone who is suffering from NASH. Having been orally administered to more than eight hundred patients to date and showing that it is useful, there is hope that people will no longer have to undergo a liver transplant.
There were no Elafibranor drug interactions detected with sitagliptin, simvastatin, or warfarin, which indicates that it could be used together with other drugs safely. Elafibranor is well tolerated in the body and doesn’t show any side effects.
- Translational Research Methods in Diabetes, Obesity, and Nonalcoholic Fatty, edited by Andrew J. Krentz, Christian Weyer, Marcus Hompesch, Springer Nature, page 261
- PPARs in Cellular and – Whole Body Energy Metabolism edited by Walter Wahli, Rachel Tee, 457-470
- Obesity and Gastroenterology, An Issue of Gastroenterology Clinics of North, Octavia Pickett-Blakely, Linda A. Lee, page 1414-1420