According to JRJ Finance APP, as the demand for Wegovy under novo-nordisk (NVO.US) and Zepbound under eli lilly (LLY.US) increases significantly in the market, concerns about the significant risk of muscle quality decline that these types of weight loss drugs may bring have also escalated. More and more biotechnology companies are actively working to address this issue.

It is reported that Wegovy and Zepbound, along with other GLP-1 drugs, have a remarkable effect on weight loss, but this weight loss to a large extent involves muscle mass. When calorie intake is reduced, not only will fat decrease, but muscle will also decrease. Although this situation is expected, some experts are concerned that this could increase the risk of injuries, especially in older people. Another concern is that a decrease in muscle mass might slow down the patient's metabolism, leading to weight regain. It is not completely clear at this point whether weight regain will correspondingly increase muscle mass.

George Yanopoulos, Chief Scientific Officer of Regeneron Pharmaceuticals (REGN.US), stated that GLP-1 drugs "may lead to continuous changes in body composition, with the disadvantages outweighing the benefits". According to George Yanopoulos, patients receiving treatment with GLP-1 drugs often experience up to 40% weight loss due to muscle loss within a year. This not only could result in an increase in body fat percentage, but more importantly, these long-term changes in body could lead to various health issues.

In order to better address this issue, Regeneron Pharmaceuticals has embarked on new drug development aimed at reducing muscle loss caused by weight loss drugs. George Yanopoulos mentioned that the company is testing a drug called trevogrumab, which aims to block the hormone that inhibits muscle growth.

Regeneron Pharmaceuticals is not the only pharmaceutical company developing myostatin-targeting drugs. In 2023, eli lilly acquired the private biopharmaceutical company Versanis Bio, whose main assets include bimagrumab. This is an investigational monoclonal antibody targeting ActRII. In a 48-week Phase II clinical trial, bimagrumab was able to cause approximately 22% fat loss in overweight or obese patients with type 2 diabetes, compared to the placebo group, and increase 4.5% in lean body mass.

Meanwhile, Biohaven (BHVN.US)'s myostatin-targeting drug taldefgrobep alfa has already shown positive preclinical data in increasing muscle mass when used in combination with GLP-1 drugs. The company announced in August that it will begin mid-stage trials for taldefgrobep alfa for obese patients in the second half of 2024.

Scholar Rock (SRRK.US) completed its Phase 2 clinical trial of the myostatin targeting drug apitegromab last month. The EMBRAZE study aimed to demonstrate the concept of preserving lean muscle mass in individuals with obesity using GLP-1 class drugs.

The company's related drugs provide different mechanisms. Keros Therapeutics (KROS.US) obesity candidate drug KER-065 aims to increase skeletal muscle and reduce fat mass by inducing the body's energy expenditure, currently in Phase 1 development stage.

BioAge Labs (BIOA.US), which just went public last month, has initiated a mid-stage study to test its main candidate drug azelaprag in combination with Eli Lilly's tirzepatide for the treatment of elderly obese patients. Preliminary preclinical studies and Phase 1 clinical studies have shown that azelaprag can improve metabolism and muscle function, significantly increase weight loss in patients treated with GLP-1 class drugs, and improve body composition and muscle function.

In addition, Veru (VERU.US) is currently in the Phase 2 trial stage with its oral therapy enobosarm, aiming to evaluate the potential of enobosarm in reducing fat and preventing muscle loss in patients receiving GLP-1 treatment.