Express significantly improves many liver indicators! Multi-target NASH innovative drug Phase 2b clinical outcomes are positive

Axcella Therapeutics today announced that AXA1125 has achieved positive interim results
in the EMMPACT clinical 2b trial for the treatment of patients with non-alcoholic steatohepatitis (NASH).
Data analysis showed that AXA1125 can help NASH patients achieve statistically significant and clinically significant improvements
in liver stiffness, inflammation and liver fat mass.

NASH is a severe, progressive liver disease
.
The cause is that the liver cannot normally metabolize lipids and carbohydrates, causing chronic inflammation caused by excessive fat accumulation in the liver, which in turn causes progressive liver fibrosis (scarring), which eventually leads to cirrhosis, and even liver failure, liver cancer and death
.
For NASH patients, advanced fibrosis is highly associated
with the risk of producing liver-related disease and death.
Each (pathogenesis) node of these diseases is affected by a specific pathway disorder, which can lead to a range of symptoms
.
Common risk factors for NASH include obesity, high blood lipids (e.
g.
, high cholesterol and triglycerides), and type 2 diabetes
.
There are currently more than 100 million NASH patients in the world, yet there are still no approved therapies
for NASH.

AXA1125 Pharmacological Mechanism (Image source: Axcella official website) AXA1125 is a multi-target oral drug candidate, which is an endogenous metabolic regulator (EMM)
combination developed by Axcella, consisting
of six amino acids and other derivatives.
These molecules are the main regulators of multiple metabolic pathways
.
By forming different combinations of them, this therapy may restore homeostasis to multiple key biological pathways, improving cellular energy efficiency
.
For example, the branched-chain amino acids (BCAAs) in this drug can promote glucose uptake, increase insulin sensitivity, and reduce lipid toxicity
.
Arginine (Arg) can reduce ammonia production and hepatocyte destruction, and glutamine (Gln) and arginine can reduce the inflammatory response
through their action on intestinal epithelial cells.
N-acetylcysteine (Nac) can produce anti-inflammatory effects
by promoting glutathione synthesis and reducing reactive oxygen species (ROS).
In February this year, the US FDA granted AXA 1125 fast-track qualification
for the treatment of NASH.
AXA1125 clinical data (Image source: Reference [3])
EMMPACT is a global, double-blind, placebo-controlled, dose-assay 2b trial to examine the safety, tolerability, and efficacy
of AXA1125 in patients treated with NASH.
This scheduled interim analysis examined data
from 82 patients at week 12 of the trial, and 58 patients at week 24.
All enrolled patients were confirmed to have grade 2 or stage NASH by biopsy, and about half of them also had type 2 diabetes
.
Enrolled patients were randomly assigned in a 1:1:1 ratio and received placebo, 22.
6 g, or 33.
9 g AXA1125
twice daily.

▲AXA1125 clinical data (image source: reference [3]) At 24 weeks, compared with the placebo group, the liver hardness measurement (LSM) of patients in the high-dose group improved significantly, and the changes in LSM in the placebo, low-dose, and high-dose groups were 0.
13, -2.
01, -4.
07 kPa (kPa) (low dose: p=0.
0992, high dose: p=0.
0096)

。 Statistically significant improvement in alanine aminotransferase (ALT) levels was seen at 12 and 24 weeks, and the difference in ALT change between -28.
61% (p=0.
0183) and -36.
3% (p=0.
0082) in the low- and high-dose groups after adjusting the values in the placebo group was -28.
61% (p=0.
0183).

In addition, significant improvements
were found in the patient's difference in liver fat content compared to baseline at 12 weeks by magnetic resonance proton density fat fraction (MRI-PDFF).
After adjusting the values of the placebo group, the liver fat content in the low and high dose groups varied to -18.
98% (p=0.
0082) and -21.
24% (p=0.
0014).

This experimental data shows that the AXA1125 has a unique targeting multi-target effect
.

AXA1125 clinical data (Image: Reference [3])
AXA1125 has also demonstrated good safety in trials, and will continue to use both doses in future trials
.
Consistent with previous trials, results are similar
for people with type 2 diabetes compared to those with non-diabetes.

"We find the results of the 12- and 24-week interim analysis very encouraging," said Mr.
Bill Hinshaw, CEO of Axcella, "and these results show that AXA1125 can achieve statistically significant improvements in metabolism, inflammation and fibrosis biomarkers at 24 weeks compared with placebo, and these findings make AXA1125 a first-line treatment for NASH
。 We will continue to conduct experiments and collect data
.
We expect to report top-line, 48-week biopsy results
in the first half of 2024.
”

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