Advancing Obesity Treatment: Pursuing Superior Weight Loss

The pharmaceutical industry is on the cusp of a breakthrough with GLP-1 agonists predicted to top sales charts by 2024. However, companies are not content with resting on their laurels and are actively seeking to refine these weight loss treatments to enhance the quality of weight reduction.

Current GLP-1 drugs have demonstrated remarkable efficacy, poised to save lives and make a significant impact, according to Paul Titchenell, a physiology professor at the University of Pennsylvania’s medical school. Yet, there are concerns. Studies indicate that a portion of the weight lost through Novo Nordisk’s Wegovy might be muscle mass, which can lead to adverse health effects, particularly in older individuals.

Titchenell notes that while the loss of muscle mass is not a significant worry for the general population, it does highlight the need for innovative approaches. The focus is on developing therapies that not only reduce weight but also preserve muscle mass.

Weight loss through traditional means typically results in a 25% loss of lean mass and 75% loss of fat mass, as stated by Scott Harris, a medical officer at Altimmune. However, in clinical trials for Wegovy, the ratio was skewed towards a higher loss of muscle mass. This is problematic, especially for the elderly, where muscle loss can lead to decreased functionality and increased health risks.

Moreover, weight loss often reaches a plateau after a year of GLP-1 drug use, potentially due to a decrease in resting metabolic rate caused by muscle loss. Companies like Eli Lilly, Altimmune, and Biohaven are exploring additional mechanisms to influence energy expenditure and enhance weight loss effectiveness.

Sustainability of weight loss induced by GLP-1 drugs is another challenge, with patients experiencing rapid weight regain after discontinuation. Titchenell suggests that maintaining muscle mass during weight loss could lead to more sustainable outcomes, an area that the pharmaceutical industry is keen to explore.

The pursuit of higher-quality weight loss has led to significant biopharma activity. Eli Lilly’s acquisition of Versanis and its drug bimagrumab, which can reduce fat mass without affecting muscle mass, is a testament to this. Bimagrumab is currently under evaluation in Phase II studies for its efficacy as a standalone treatment or in combination with other drugs.

Biohaven is also initiating trials for its drug taldefgrobep, which is already being tested for spinal muscular atrophy, indicating a well-established safety profile. Analysts are looking forward to seeing the endpoints of these trials, as the traditional measure of total body weight loss may not fully reflect the efficacy of these new formulations.

Altimmune is investigating pemvidutide, a drug that targets both GLP-1 and glucagon receptors, aiming to reduce appetite and increase energy expenditure while preserving lean mass. In trials, pemvidutide has shown promising results in weight loss and reduction of serum lipids and liver fat.

The market is expected to differentiate between various mechanisms of action to cater to specific patient needs. While existing drugs like Wegovy and Zepbound have a solid customer base, there is room for new drugs that address the needs of obese patients with dyslipidemia. The future of obesity treatment is likely to involve synergistic mechanisms that preserve muscle and achieve maximum weight loss, potentially leading to sustainable weight loss where the need for continuous medication is reduced.