The next billion-dollar market for weight-loss miracle drug GLP-1 - NASH

The miraculous drug Semaglutide is well-known in the field of weight loss, and has made GLP-1 a star target. However, the potential therapeutic effects of GLP-1 go far beyond diabetes and weight loss. NASH (non-alcoholic fatty liver disease) has become the next competitive focus of GLP-1.

NASH is the next step of the famous fatty liver

When it comes to NASH, many people may be unfamiliar with it, but when it comes to fatty liver, it is very familiar. Yes, NASH is the next step in the development of fatty liver.

Fatty liver has become the most common signal of physical abnormalities in medical examinations, and if left unchecked, it may develop into NASH, liver fibrosis, cirrhosis, and even liver cancer. NASH has faced the challenge of having no cure for several decades.

Generally speaking, the fatty liver we refer to is the lightest form of non-alcoholic fatty liver disease (NAFLD), which is simply fatty degeneration of the liver (without inflammatory fat deposition). In this form, liver cells coexist peacefully with fat.

NASH (non-alcoholic steatohepatitis) is a severe type of NAFLD (non-alcoholic fatty liver disease), defined as liver fat degeneration of more than 5%, combined with inflammation and liver cell damage, with or without fibrosis.

In layman's terms, liver cells and fat are no longer compatible at this stage, and they begin to attack each other. Fat produces a large amount of toxic lipid metabolites, causing liver cell damage. In order to clear the foreign substances, damaged liver cells release cytokines, which in turn produce a large amount of inflammatory factors, stimulating new inflammation and damage. The liver cells undergo programmed death during the process of clearing foreign substances.

But the real trouble comes later. Liver cells can regenerate, but they become disordered and disorganized in the process of repeated inflammatory reactions and repair, accompanied by the production of a large amount of useless fibrous connective tissue. Over time, the liver will be filled with this connective tissue, forming fibrosis and cirrhosis, while repeated liver cell regeneration greatly increases the risk of cancer.

NASH has become one of the most urgent unmet clinical needs in the world, with huge market potential.

According to Foster Sullivan's prediction, the market capacity of NASH drugs will exceed 10 billion US dollars by 2025, with a compound annual growth rate of 20.19% from 2016 to 2025.

NASH - the next competitive field of GLP-1

As researchers delve deeper into the study of GLP-1 targets, they have found that GLP-1 can reduce liver fat degeneration, liver cell damage, and glucose output after binding to liver cell receptors, and can reduce liver cell inflammatory reactions and fibrosis in NASH.

Currently, the fastest progress in the field of NASH is also the weight loss miracle drug Semaglutide. According to the announcement by Novo Nordisk, semaglutide has shown positive results in the treatment of NASH in Phase 2 clinical trials. Among patients receiving the highest dose of semaglutide, 66.7% had their NASH symptoms eliminated. In terms of improving liver fibrosis in patients, among those receiving the highest dose of semaglutide, 5.8% had progression of liver fibrosis (compared to 21.4% in the placebo group). Currently, a Phase 3 international multicenter clinical trial of semaglutide for NASH has been launched in China.

Of course, other competitors have also been attracted to the NASH field. As a company that is relatively behind in the fields of diabetes and weight loss, Merck has taken a different approach and chosen NASH as an indication for competition.

Today, Merck announced that its GLP-1R/GCGR dual-target agonist Efinopegdutide has recently been granted fast track qualification by the FDA for the treatment of NASH. It is worth noting that other clinical trials with the same target in NASH include Cotadutide from AstraZeneca and BI456906 from Boehringer Ingelheim.

At the same time as Merck announced that Efinopegdutide had been granted fast track qualification by the FDA, it also announced that it would report on the Phase 2a clinical data of Efinopegdutide for the treatment of NAFLD at the EASL conference to be held on June 21-24.

Earlier, on June 7, Merck updated the design of the Phase 2b clinical trial of Efinopegdutide for NASH on Clinicaltrials.

According to the plan, 300 people will be enrolled in Phase 2b. It is worth noting that Merck has chosen two control groups for Efinopegdutide, one is the conventional placebo group, and the other is the well-known semaglutide.

Compared with the clinical trial of semaglutide in Phase 2a, the dose of semaglutide in Phase 2b will be further increased, from a maximum of 1 milligram to a maximum of 1.7 milligrams, and the duration of treatment will be further extended from 24 weeks to 36 weeks.

Merck's clinical design shows two issues.

On the one hand, the company believes that semaglutide is expected to be the first to be approved globally for NASH indications.

Jianzhi Research believes that if semaglutide is approved first, the medication guidelines for NASH will change. If other companies in development still use placebos as clinical control groups, they will face the risk of not being able to market their products. Prior to this, the electric field tumor therapy introduced by Zaiding encountered this problem in lung cancer. The clinical trial was conducted with chemotherapy as the control group, but the drug guidelines were changed to K drugs before listing. In addition to non-small cell lung cancer, many drugs under development in other indications also face the same dilemma.

On the other hand, it also shows that Merck is more confident in its dual-targeted drugs and can beat semaglutide in a head-to-head competition, and obtain potential best-in-class products.

Therefore, from this clinical design, Jianzhi Research believes that the clinical design of large pharmaceutical companies has more rigor and judgment on future markets.

In addition to GLP-1, THR-β, FGF, etc. have also demonstrated potential in NASH.

In December last year, Madrigal Pharmaceuticals, a US stock company, announced that its THR-β agonist Resmetirom for the treatment of NASH in Phase 3 trials was successful.

Jianzhi Research mentioned in its previous article "The world's first NASH new drug exceeded expectations and succeeded, the billion-dollar field, who in China can keep up?" that from the perspective of the THR-β target, the only one in China that has entered clinical trials is Geely Pharmaceutical's ASC41. The company started to verify this target 5 years ago, and the progress is currently ranked first in China and third in the world.

89bio, which has performed well in the capital market this year, is a representative of the FGF target. The proportion of NASH relief and fibrosis without deterioration in the 44mg Q2W and 30mg QW dose groups was 26% and 23%, respectively, which was 12-14 times that of the placebo group (2%).

As good news of clinical drugs from various targets came, the NASH field, which had no drugs available for decades, will finally have new drugs available.

In summary, the GLP-1 target has achieved great success in the field of weight loss, but the future of GLP-1 is far more than weight loss. With the progress of clinical research, the next competition in the billion-dollar NASH field will come.