The mid-term results of RNAi therapy are positive, which may break the non-alcoholic steatohepatitis (NASH) drug-free situation

HPN-01 is a new molecular entity drug independently developed by Hepuchem to treat NASH and liver fibrosis
.
Its target and mechanism are different from all NASH candidate new drugs currently in clinical development, and its differentiated competitive advantage is obvious
.
Compared with other NASH drugs under research with a single target and mechanism of action, HPN-01 can regulate and block multiple important pathways for the occurrence and development of NASH, which can effectively reverse liver steatosis and alleviate inflammatory reactions in the liver.
Lipid peroxidation, thereby improving liver fibrosis and liver dysfunction
.

Biological studies conducted by Hepperchem Laboratories and cooperative research institutions at the cellular and animal levels have shown that HPN-01 effectively inhibits multiple key molecular pathways that regulate fat metabolism, inflammation, and fibrosis in the liver, thereby significantly alleviating and blocking Hepatic steatosis and fibrosis are severed
.
The in vivo efficacy of NASH and related complications has been verified in multiple animal models, and the results of systematic toxicology studies show that the drug has excellent safety
.
Phase I clinical trials are currently underway
.

03 THR-β agonist

Thyroid hormone beta receptor (THR-beta) is the industry's more promising target for NASH
.
In recent years, the clinical research of Madrigal Pharmaceuticals' THR-β agonist Resmetirom (MGL-3196) has progressed relatively smoothly, and two phase 3 clinical studies of MAESTRO-NASH and MAESTRO-NAFLD-1 are currently underway
.

The follow-up analysis of the Phase 2 clinical study data released last year showed that the reduction of liver fat 3 months after MGL-3196 treatment has obvious predictive power for the regression of NASH and the reversal of fibrosis obtained by subsequent liver biopsy
.
The interim data of the MAESTRO-NAFLD-1 study published recently showed that 80% of patients in the 100mg treatment group had liver fat lower than baseline by at least 30%, and at week 16, more than 50% of patients had liver fat lower by at least 50%
.
The 30% and 50% reduction of liver fat is related to the regression of NASH and the reversal of liver fibrosis during liver biopsy
.

04 SCD-1 inhibitor

Aramchol is a new synthetic small molecule developed by Galmed Pharmaceuticals.
It is a compound of cholic acid and arachidic acid linked by a stable amide bond.
It exerts its anti-stearic acid by inhibiting the expression of SCD-1 in hepatocytes and hepatic stellate cells.
The role of chemical and anti-fibrosis
.
Data from its Phase 2 study on the treatment of NASH showed that Aramchol can reduce liver fat content, improve liver histological characteristics, liver biochemical indicators and blood glucose parameters, and has good safety and tolerability
.

In addition, in May 2020, Novo Nordisk announced that the hypoglycemic drug Semaglutide has achieved positive results in a phase 2 clinical trial for the treatment of NASH
.
Compared with placebo, semaglutide can significantly eliminate the histological symptoms of NASH in patients without exacerbating liver fibrosis
.

In the same year, Junshengtai announced that its original innovative drug HTD1801 in the phase 2a clinical trial of patients with NASH and type 2 diabetes reached the primary endpoint and multiple important secondary endpoints.
It has significant benefits in removing liver fat, including liver enzymes, blood sugar, and Blood lipids, body weight and other aspects have shown comprehensive control effects, showing good efficacy and safety
.
Jun Shengtai will start a Phase 2b study on NASH in 2021
.

At present, Fujian Guangshengtang GST-HG151, Zhengda Tianqing TQA3563, Dongyang Sun Pharmaceutical HEC96718, etc.
are still in clinical phase I in China
.

Research AndMarkets previously released a report that pointed out that the NASH market was US$729 million in 2016 and is expected to reach US$20.
676 billion by 2025.
The compound annual growth rate from 2017 to 2025 will reach an astonishing 46.
1%
.

Although the medical needs are huge, NASH still has no effective drugs approved for treatment, and only through life>
.

At present, some of the world's large pharmaceutical companies, including domestic pharmaceutical companies, have deployed in this field one after another
.
I believe that with the unremitting efforts of Chinese and foreign pharmaceutical companies, we will eventually overcome the difficulties and obstacles on the road of NASH research and development, and develop effective and safe NASH drugs to benefit the majority of NASH patients
.

reference:

1.
Abstract: ARO-HSD reduces hepatic HSD17B13 MRNA expression and protein levels in patients with suspected NASH (LBP-2580);

2.
Pharmacotherapy for NASH: Current and emerging;

3.
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity.
Nature 482, 179-185(2012);

4.
New drugs for NAFLD: lessons from basic models to the clinic.
Hepatol Int 2020 Jan;14(1):8-23;

5.
A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement.
Journal of Hepatology 2020 vol.
73j 202–209.