Alnylam Pharmaceuticals and its partners have identified rare mutations in the INHBE gene that is expressed in the liver and related to a lower waist-to-hip ratio for body mass index (BMI) reducing the likelihood of many major metabolic disorders. With such high levels of interest preventing metabolic disorders, it is likely that a drug which holds a capacity to demonstrate high efficacy in targeting INHBE expression will gain a significant market share as it could help in reducing the risk significantly for multiple metabolic disorders, says GlobalData, a leading data and analytics company.

Using the UK Biobank, Alnylam was able to search gene variants that were associated with lower waist-to-hip ratio adjusted for BMI, which is often used as an indicator of abdominal fat and is correlated to risk of type 2 diabetes (T2D) and coronary heart disease, and identified that the mutated INHBE gene can be found in 1 in 587 individuals. The company plans to leverage its RNAi platform to develop a pipeline candidate that targets INHBE and Activin E.

Akash Patel, Pharma Analyst at GlobalData, comments: “There is a significantly increasing body of evidence relating obesity to T2D and related metabolic disorders such as coronary heart disease and heart failure (HF). Several therapies have emerged in the last five to 10 years, particularly in the glucagon-like peptide-1 receptor agonist (GLP-1) class, that address obesity and decrease cardiovascular risk in addition to leading to improved HbA1c for patients with T2D.”

In particular, semaglutide (Rybelsus and Ozempic) from Novo Nordisk and tirzepatide (Mounjaro) from Eli Lilly have rapidly become the market-leading therapies for patients with T2D and obesity.

Patel adds: “As the late-stage clinical studies have shown Mounjaro has the ability to transform the treatment of obesity, in addition to T2D. The drug will likely be prescribed in combination with other therapies to address additional cardiorenal problems and will progress to becoming a leading GIP/GLP-1 therapy. Furthermore, trials for pediatric patients and heart failure patients are currently ongoing, which will also strengthen Lilly’s position across the wider T2D and cardiometabolic market.”