U.S. first possible NASH therapy

Madrigal Pharmaceuticals succeeded in three phases of Resmetirom, a candidate substance

Domestic pharmaceutical development speed due to technology transfer and self-clinical, etc

↑Expectations for the first NASH treatment

The U.S.

 

Madrigal Pharmaceuticals has succeeded in phase 3 clinical trials of Resmetirom, a new drug candidate for non-alcoholic fatty hepatitis (NASH).

 

When new drugs are approved, Resmetirom appears as the first NASH treatment aimed at the 33 trillion won market.

 

Yuhan Corporation, Hanmi Pharmaceutical, and LG Chem are also speeding up the development of NASH new drug candidates through technology transfer or its own clinical progress.

 

On the 20th, Madrigal Pharmaceuticals announced that it has secured a positive top line in phase 3 clinical trials (MAESTRO-NASH), which studies Resmetirom as a NASH treatment.

 

Resmetirom is a thyroid hormone receptor (THR)-beta agonist administered orally.

 

NASH is a disease in which fat accumulated in the liver develops into inflammation, causing liver fibrosis and cirrhosis.

 

It is highly likely to develop in obese and diabetic patients.

 

According to Evaluate Pharma, a pharmaceutical market research company, the NASH treatment market is expected to grow more than 20 times from 277.1 billion won this year to 6.723 trillion won by 2026.

 

It is expected to expand to 33 trillion won by 2030.

 

Phase 3 clinical trials are a study that analyzes efficacy and safety for up to 54 months after administering Resmetirom 80 mg/100 mg and placebo for 52 weeks in 955 patients with confirmed NASH.

 

The first evaluation index is "the standard for resolving more than two points of fibrosis without worsening liver fibrosis" and "the standard for improving the first stage without worsening fibrosis." It was effective in both the 80 mg and 100 mg groups.

 

The clinical trial was successfully completed by obtaining statistical significance compared to the placebo group.

 

The secondary evaluation indicators are 'whether LDL cholesterol decreases at week 24' and 'based on liver enzymes'.

 

The 80 mg group and the 100 mg group reduced LDL cholesterol by 12% and 16%, respectively, to obtain statistical significance.

 

The placebo group increased by 1%.

 

A significant decrease was also confirmed in the liver enzyme standard.

 

Compared to placebo, it was confirmed that fibrosis decreased through biomarkers and imaging tests in the Resmetirom treatment group.

 

Resmetirom was safe and drug resistant in both 80 mg and 100 mg doses.

 

The frequency of severe side effects (SAEs) was similar across the target group, with each group showing around 12%.

 

Paul Freedman, CEO of Madrigal Pharmaceuticals, said, "This clinical trial is reasonably likely to predict Resmetirom benefits and has achieved both major indicators proposed by the U.S.

 

Food and Drug Administration," adding, "We will submit an application for a new drug to approve resmetirom acceleration in the first half of 23." Domestic pharmaceutical companies are also speeding up the development of NASH treatments.

 

Yuhan Corporation signed a technology transfer contract with global pharmaceutical companies Beringer Ingelheim and Gilead, respectively, in 2019.

 

NASH's new drug candidate "YH25724," which was transferred to Beringer Ingelheim, is undergoing phase 1 clinical trials in Europe.

 

YH25724 is a candidate material developed by Yuhan Corporation.

 

In this process, it is a fusion protein that combines "Hybrid FC" (HyFc), an antibody fusion protein platform technology of bio company Genexine.

 

There are two types of synthetic materials transferred to Gilead, Yuhan Corporation and Gilead will jointly conduct non-clinical research, and Gilead will conduct global clinical trials.

 

Hanmi Pharmaceutical transferred NASH's new drug candidate "Dual Agonist" to MSD in 2020.

 

MSD has been undergoing phase 2 global clinical trials since last year.

 

Another candidate substance, LAPSTriple Agonist, was also designated by the FDA as a fast track development drug for NASH treatment.

 

If it is designated as a fast-track drug, it can have close consultations with the FDA at each stage of development and receive full support.

 

LG Chem is developing its own NASH new drug candidate "LG203003" through the LG Chem Life Science Innovation Center in Boston, USA.

 

In March, the FDA approved a phase 1 clinical plan (IND).

 

In July, phase 1 was launched for 88 healthy adults and NASH patients to observe safety and drug resistance, pharmacokinetics, pharmacology, and changes in fat volume in the liver.

 

LG203003 is a mechanism that suppresses fat accumulation in liver cells by selectively interfering with the activation of DGAT-2, a neutral fat synthase.

 

LG Chem also has another NASH candidate, 'LG303174.

 

It inhibits the expression of VAP-1 protein, which is known to affect inflammation in the liver.

 

In August 2020, LG Chem signed a technology transfer contract from TransThera Biosciences in China to introduce LG303174's right to global development and commercialization.