In proof-of-concept trial, daily pill lowers blood, liver fat levels in MASLD
TLC-2716 tested in overweight adults with liver disease in Mexico
Written by |
Daily treatment with Orsobio’s oral candidate TLC-2716 reduces fat levels in both the blood and liver in overweight adults with high blood fat levels and metabolic dysfunction-associated steatotic liver disease, or MASLD.
That’s according to top-line data from a proof-of-concept Phase 2a clinical trial (NCT06564584) that involved 30 participants and tested the experimental therapy versus a placebo.
“These results support continued development of TLC-2716 across multiple severe metabolic disorders, which collectively affect millions of patients worldwide,” Rob Myers, MD, chief medical officer and head of development for Orsobio, said in a company press release announcing the trial’s results.
“We look forward to presenting a comprehensive dataset at a future scientific conference to provide a more detailed characterization of the therapeutic profile of TLC-2716,” Myers added.
MASLD is a form of steatotic liver disease (formerly called fatty liver disease) that is marked by the abnormal buildup of liver fat in people who typically have cardiometabolic risk factors, such as obesity, high blood fat levels, and diabetes.
Left unchecked, a buildup of liver fat in some people can lead to an advanced form of the disease called metabolic dysfunction-associated steatohepatitis (MASH). This is marked by inflammation and scarring that damages the liver and sets the stage for serious complications, including liver cancer.
TLC-2716 is designed to decrease the activity of the liver X receptor (LXR), a protein that helps to regulate how the body processes triglycerides and cholesterol, two types of fatty molecules.
The investigational oral therapy, which specifically targets LXR in the gut and liver, aims to lower fat levels by simultaneously reducing fatty molecule production in the liver, increasing their clearance in the body, and decreasing their intestinal absorption.
Study’s main goal was to assess safety, impact on triglycerides
Data from a previous New Zealand-based Phase 1 clinical trial (NCT05483998), which involved healthy volunteers, showed that TLC-2716 was well tolerated and reduced blood levels of triglycerides and remnant cholesterol. This type of cholesterol is associated with cardiovascular issues such as stroke and heart disease.
This Phase 2a study, conducted in Mexico, enrolled 30 adults with MASLD who were overweight and had hypertriglyceridemia, or high blood levels of triglycerides. The participants were randomly assigned to take either one of two doses of TLC-2716 — 6 mg or 12 mg — or a placebo, once daily for about a month.
The study’s main goals were to evaluate the safety of TLC-2716 and its impact on blood triglyceride levels in a fasting state, or 9-12 hours after the person’s last meal.
The results showed that both doses of TLC-2716 “resulted in clinically meaningful and statistically significant reductions in fasting triglycerides” relative to the placebo, the release stated.
The substantial reductions in triglycerides, … cholesterol, and other [blood vessel-damaging fatty molecules] — along with improvements in liver fat and a favorable safety profile — support the potential of TLC-2716 to become a meaningful therapeutic option for patients with … MASH.
Treatment was also associated with reductions in liver fat content and in blood levels of remnant cholesterol and other fatty molecules known to damage blood vessels and increase the risk of cardiovascular disease.
The researchers noted that fatty molecule reductions were particularly pronounced in participants with more severe hypertriglyceridemia (at least 500 mg/dL of triglycerides) at the study’s start.
In the proof-of-concept study, TLC-2716 was generally tolerated well, with no serious safety concerns reported.
“The substantial reductions in triglycerides, remnant cholesterol, and other [blood vessel-damaging fatty molecules] — along with improvements in liver fat and a favorable safety profile — support the potential of TLC-2716 to become a meaningful therapeutic option for patients with diseases driven by excessive [fatty molecule] production, including [severe hypertriglyceridemia], MASH, and elevated remnant cholesterol,” Myers said.
Overall, he added, the data “provide compelling clinical validation of [targeting LXR] as a differentiated therapeutic strategy for severe metabolic disorders.”
