Pegozafermin Emerges as a Strong Competitor to Resmetirom in the Race to Treat NASH

The Race to Develop NASH Treatment: Pegozafermin Shows Promising Results

In the competitive field of developing a treatment for non-alcoholic steatohepatitis (NASH), Pegozafermin, developed by 89BIO, is gaining ground on the leading contender, Resmetirom. While Resmetirom recently presented positive phase 3 clinical trial results, showing improvements in fibrosis and the eradication of NASH, Pegozafermin has demonstrated superior efficacy in phase 2 trials.

Recently, researchers, including Rohit Loomba from the NAFLD Research Center of the University of California Medical School, published their findings on the administration of the FGF21 analogue pegozapermin to NASH patients in the esteemed international journal NEJM. FGF21 is a metabolic hormone that plays a crucial role in regulating energy expenditure and glucose and lipid metabolism by acting on Fibroblast Growth Factor 21 (FGF21).

The results of the phase 2 clinical trial involving 219 patients with biopsy-proven NASH and stage F2-F3 liver fibrosis were particularly promising. Patients were randomly assigned to receive either 15/30 mg weekly, 44 mg weekly, or a placebo every 2 weeks for 24 weeks. The primary endpoint of the study was to assess fibrosis improvement, and secondary endpoints included evaluating the eradication rate of NASH and the drug’s safety profile.

The analysis of the trial results revealed that the proportion of patients showing improvement in fibrosis was significantly higher in the groups receiving Pegozafermin compared to the placebo group. Similarly, the percentage of patients meeting the criteria for NASH remission was notably higher in the Pegozafermin groups. Adverse reactions to the treatment were primarily restricted to nausea and diarrhea.

The research team concluded that Pegozafermin demonstrated significant improvement in fibrosis, supporting the need for phase 3 clinical trials. Notably, Pegozafermin surpassed Resmetirom in terms of fibrosis improvement rate, further highlighting its competitive advantage. To be approved by the FDA as a NASH treatment, a drug must demonstrate either fibrosis improvement or NASH eradication rates. Pegozafermin satisfies both criteria, despite still being in phase 2 clinical trials.

Experts in the field are optimistic about the potential of various candidates in improving fibrosis and preventing NASH. With different mechanisms and modes of administration, including oral and injectable options, the effectiveness of these treatments will need further investigation in large-scale clinical trials.

As the race to find a suitable NASH treatment continues, the medical community eagerly awaits the outcomes of these trials. Only time will tell which drug or combination of drugs will emerge victorious in the fight against NASH.

Pegozafermin, which is being developed by 89BIO in the development of NASH (non-alcoholic steatohepatitis), which has about 130 clinical pipelines in operation worldwide, is closely chasing the leading Resmetirom.

Resmetirom moved one step closer to commercialization by presenting phase 3 clinical trial results that improved fibrosis and achieved eradication of NASH, but Pegozafermine gained an edge over Resmetirom in terms of efficacy through phase 2 clinical trials.

According to the medical community on the 28th, the results of the FGF21 analogue pegozapermin administration to NASH patients carried out by researchers including Rohit Loomba from the NAFLD Research Center of the University of California Medical School in the United States were published in the international journal NEJM (DOI : 10.1056/NEJ Moa2304286 ).

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FGF21 is an endogenous metabolic hormone that regulates energy expenditure and glucose and lipid metabolism. It has a mechanism involved in the regulation of glucose and lipid homeostasis by acting on FGF (Fibroblast growth factor)21.

Pegozapermine showed a strong reduction in fatty liver and a clinically meaningful response in a significant proportion of patients. In addition, results suggestive of changes in major liver markers associated with NASH have been observed, and it is emerging as a drug that improves liver pathology and resolves underlying metabolic problems.

In the phase 2 clinical trial, 219 patients with biopsy-proven NASH and stage F2-F3 liver fibrosis (moderate or severe) were randomly assigned to receive 15/30 mg weekly, 44 mg weekly, or placebo every 2 weeks for 24. weeks.

The primary study endpoint was improvement in fibrosis (grade 0-4, higher score, worse), and NASH eradication rate and safety without NASH or worsening fibrosis were also evaluated.

As a result of the analysis, the proportion of patients who fulfilled the criteria for improvement of fibrosis was 7% in the placebo group, 22% in the pegozafermin 15 mg group (14% difference compared to placebo), 26 % at 30mg. 19%po difference), and 27% at 44mg (19%p difference) With a 20%p difference), pegozapermine was effective in a dose dependent manner.

The percentage of patients meeting NASH remission criteria was also 2% in the placebo group, 37% in the pegozapermin 15 mg group (35% difference c compared to placebo), 23% on 30mg (21% difference c) , and 26% at 44mg (24%p difference). %p) shows a similar pattern.

The most common adverse reactions associated with pegozapermine treatment were nausea and diarrhea.

The research team concluded, “Through the phase 2b clinical trial using pegozapermin, improvement in fibrosis was confirmed,” and “these results support the need for phase 3 clinical trials.”

To be approved by the FDA as a NASH treatment, one of the fibrosis improvement or NASH eradication rates must be met, but pegozappermine meets both of these, and is said to have confirmed its competitiveness despite only it is in a phase. 2 clinical trials.

In particular, looking at the response rate of the treatment group compared to the response rate of the placebo group, the fact that pegozapermine was ahead of Resmetirom in the rate of improvement of stage 1 or higher fibrosis (19/20% versus 10/). 12%) is also a factor that highlights its competitiveness.

An official from the Society for the Study of the Liver said, “It is encouraging to see that various candidates are effective in improving fibrosis and preventing NASH in the absence of a suitable NASH treatment yet.” Each one has a different mechanism and method. Administration is divided into oral and injection, so we have to wait and see what will be effective.”

He said, “Resmetirom has more than 300 people in each dose group, but clinical trials for other ingredients are relatively small, so the key is whether similar effects can be reproduced in additional clinical trials involving large-scale people or not.” , Efforts to divert candidates from the obesity treatment mechanism to NASH treatments are also ongoing, so we have to wait and see the results.”

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