GLP-1 uses↑…targets MASH, diabetes, and obesity

Novel drug candidates of GLP-1 from Novo Nordisk, Boehringer Ingelheim, and Lily show achievements in phase 2 trials

Dong-A ST and D&D pharmatech present new clinical trial outcomes

New drug candidates of the GLP-1 class target metabolic dysfunction-associated steatohepatitis (MASH) in addition to diabetes and obesity.

 

Global pharmaceutical companies, such as Novo Nordisk, Eli Lily, Boehringer Ingelheim, and Korean pharmaceutical companies, including Dong-A ST and D&D pharmatech, are developing GLP-1 agents for the treatment of MASH.

 

GLP-1 can aid weight loss by increasing fullness and can enhance blood glucose control by increasing insulin secretion and sensitivity.

 

Weight loss can have a positive impact on patients, as MASH occurs when fat saturates in the liver of individuals who have had low or no alcohol consumption.

 

Nonetheless, pharmaceutical companies are working on the potential of GLP-1 for the treatment of MASH in addition to diabetes and obesity.

 

New drug development for MASH by multinational pharmaceuticals companies.

 

(from the top) Madrigal Pharmaceuticals’ Rezdiffra, Intercept Pharmaceuticals’ Ocaliva, Galmed Pharmaceuticals’ Aramchol, Novo Nordisk’s semaglutide, akero’s efrixiferm, Regeneron Pharmaceuticals and Alnylam Pharmaceuticals’ ALN-HSD, Viking Therapeutics’ VK2809, and others.

According to industry sources on June 12th, Boehringer Ingelheim’s 'survodutide' and Lily’s 'Tirzepatide' demonstrated the effectiveness in Phase 2 clinical trials.

 

These two new drug candidates are a type of glucagon-like peptide 1 (GLP-1).

 

In a Phase 2 trial, survodutide, targeting both GLP-1 and glucagon, showed effects in the percentage of symptom worsening at 48 weeks compared to the placebo.

 

This trial assessed the Survodutide’s effectiveness in 295 adults with MASH and liver fibrosis regardless of having type 2 diabetes.

 

Based on recent clinical results, the percentange of patients who significantly improved in MASH-associated liver diseases withought worseninig of fibrosis stage was 83% in the survodutide treatment group, whereas 18.2% in the placebo group.

 

The survodutide treatment group also had a higher percentage of patients with decreased liver fat over 30%, compared to the placebo.

 

Eli Lily also confirmed the effectiveness of tirzepatide in a phase 2 trial for MASH.

 

Tirzepatide is a GLP-1·GIP dual targeting agent with the same ingredient as Lily’s type 2 diabetes drug Mounjaro and obesity drug Zepbound.

 

The SYNERGY-NASH Phase 2 trial, evaluating the effectiveness of tirzepatide, involved 190 MASH patients who have biopsy-confirmed moderate-to-severe fibrosis.

 

At 52 weeks, established as the primary endpoint, the percentage of symptom improvement without worsening fibrosis was 43.6%, 55.5%, and 62.4% for tirzepatide 5 mg, 10 mg, and 15 mg, respectively.

 

Korean companies show progress in MASH clinical trials

New drug development for MASH by pharmaceutical companies based in South Korea.

 

(from the top) Hanmi Pharm’s efocipegtrutide, Dong-A ST’s DA-1241 and DA-1726, HK inno.

 

N’s FM-101, D&D pharmatech’s DD01, Yuhan’s YH25724, Ildong Pharmaceutical’s ID119031166, LG Chem’s LG303174 and LG203003.

Korean companies are also focusing on the potential of GLP-1.

 

Dong-A ST is developing DA-1241 with an underlying mechanism of GPR119, a receptor on beta cells in the pancreas, and is also considering the potential for combination therapy with a GLP-1 agent.

 

Neurobo, Dong-A ST’s subsidiary, recently confirmed the effect of semaglutide in combination with a MASH novel drug candidate, DA-1241.

 

Dong-A ST is exploring the potential of semaglutide, a GLP-1 agent, as a combination therapy in addition to its phase 2 trial for DA-1241 monotherapy.

 

The trial evaluated the efficacy and safety of administering DA-1241 in combination with semaglutide in a metabolically altered MASH mouse model.

 

The clinical results showed that mice treated with combination therapy improved NAS (liver fat activity score) by greater than a score of 1.

 

Furthermore, the genetic analysis of liver tissue showed that the combination therapy significantly improved the expression of genes related to inflammation and fibrosis.

 

Dong-A ST plans to make clinical entry for the combination therapy and present global phase 2 trial results on DA-1241 monotherapy.

 

D&D pharmatech is conducting a phase 2 trial in the United States.

 

The company recently received IND approval from the U.S.

 

Food and Drug Administration (FDA).

 

In preclinical trials, D&D pharmatech’s DD01, an agent targeting both GLP-1 and glucagon, has shown a significant decrease in liver fat and a weigh loss effect.

 

In a phase 1 trial, the four-week treatment of DD01 reduced the liver fat by 50%.

 

DD01’s phase 2 trial will be conducted across 10 institutes in the United States, enrolling 68 patients with MASH-accompanying overweight and obesity.

 

'Rezdiffra,' the only commercially available MASH treatment has an underlying mechanism of targeting thyroid hormone receptor The only drug commercialized for MASH treatment is Rezdiffra from the U.S.-based Madrigal Pharmaceuticals.

 

The drug targets the thyroid hormone receptor (THR)-β.

 

The U.S.-based Viking Therapeutics also conducted a phase 2b trial for a pharmaceutical with a similar mechanism to Rezdiffra and recently secured a positive result.

 

In the clinical trial, Viking Therapeutics’ MASH candidate, known as VK2809, has significantly reduced liver fat.

 

In the clinical trial VOYAGE, up to 75% of VK2809 treatment group had a MASH response, compared to 29% of the place group.

 

The adverse reactions associated with the VK2809 treatment were mostly mild or moderate.