Novo Nordisk Strategically Optimizes Obesity Pipeline by Halting Two Early-Stage Drug Candidates

Author | Xiao Yaowan

Recently, Novo Nordisk’s Q2 performance report announced the termination of development for two investigational new drug programs: a glucagon/GLP-1 receptor co-agonist and a triple full agonist targeting GLP-1, gastric inhibitory peptide, and glucagon receptors. Both drugs were being developed for the indication of obesity.

Over the past two years, Novo Nordisk has collaborated with multiple leading companies in the fields of cardiovascular disease, non-alcoholic steatohepatitis (NASH), chronic kidney disease, and innovative therapies, continuously expanding its portfolio of products for chronic disease management. Notably, the voluntary termination of the development of two investigational new drugs for obesity was not due to clinical failure, but rather driven by the positive results obtained from two other drug candidates in obesity studies.

Novo Nordisk’s Expanded Pipeline of New Drugs for Obesity Treatment

In the field of glucose-lowering medications, Novo Nordisk has been exploring for over 30 years, committed to developing safe and effective GLP-1 receptor agonist products.

In late December 2014, Novo Nordisk’s diabetes drug liraglutide received FDA approval for the treatment of adult patients with obesity who have a body mass index (BMI) ≥30 kg·m⁻², or a BMI ≥27 kg·m⁻² with at least one weight-related comorbidity such as diabetes or hypertension, thereby adding a new product to its obesity portfolio.

In the GLP-1 field, its long-acting product, semaglutide, has demonstrated superior efficacy in glycemic control and weight reduction in previous studies. This medication facilitates weight loss by suppressing hunger and enhancing satiety, thereby helping individuals consume less food and reduce their caloric intake. Novo Nordisk is investigating the use of once-weekly semaglutide 2.4 mg for the treatment of obesity in adults.

Beyond the GLP-1 space, Novo Nordisk is investigating AM833 for weight management in patients with obesity or overweight who have at least one weight-related comorbidity. AM833 is a long-acting human amylin analog that reduces body weight by decreasing energy intake.

Novo Nordisk Voluntarily Terminates Development of Two Investigational Obesity Drugs, Primarily Based on Positive Clinical Results from Two Studies Related to AM833 for the Treatment of Obesity. In particular, clinical data from the combination of AM833 and semaglutide further strengthen Novo Nordisk’s obesity portfolio and have the potential to bridge the gap between pharmacotherapy and bariatric surgery. By proactively discontinuing these new drug development programs, Novo Nordisk is concentrating its core resources to accelerate the market launch of semaglutide and AM833 in the field of obesity treatment.

Good News from Two Clinical Studies of AM833

On June 18, Novo Nordisk announced the primary results from two clinical trials of AM833, a novel amylin analog administered via once-weekly subcutaneous injection: a Phase II monotherapy study and a Phase I study evaluating AM833 in combination with 2.4 mg of once-weekly subcutaneous semaglutide.

The Phase II clinical study of AM833 monotherapy enrolled 706 patients with obesity or overweight who had at least one weight-related comorbidity. The 26-week study included five different weekly dose groups and aimed to evaluate the safety, tolerability, and efficacy of AM833 for weight management.

The study met its primary clinical endpoint. At 26 weeks, patients in the AM833 4.5 mg dose group achieved a 10.8% reduction in body weight from a mean baseline of 107.4 kg, compared with a 3.0% reduction in the placebo group; the treatment difference was statistically significant. Meanwhile, AM833 demonstrated a favorable safety and tolerability profile.

The Phase I clinical study of AM833 in combination with semaglutide enrolled 80 patients with obesity or overweight, lasting for 20 weeks, aiming to observe the safety, tolerability, pharmacokinetic characteristics, and weight loss potential of AM833 combined with semaglutide 2.4 mg.

At the end of the trial, the mean baseline body weight of subjects receiving the highest dose was 95.5 kg, with a mean weight reduction of 17.1% after 20 weeks of treatment.

Potential Therapeutic Market for Obesity Treatment Drugs

Obesity is a chronic metabolic disease caused by multiple factors, characterized by an increase in the volume and number of adipocytes, and accompanied by various complications. This chronic condition requires long-term management and can lead to many serious health consequences and reduced life expectancy.

Globally, several drugs previously approved for the treatment of obesity, such as amphetamines and sibutramine, have been withdrawn from the market due to various serious side effects. To date, orlistat remains the only drug approved in China for the treatment of obesity; this gastrointestinal and pancreatic lipase inhibitor generated sales of RMB 300 million in the Chinese market in 2018.

Notably, obesity is gradually becoming an increasingly severe problem. By the end of 2019, there were nearly 700 million people with obesity worldwide, and the vast majority of patients did not receive effective pharmacological treatment, indicating a huge market demand in this field.

Focusing on the Chinese market, domestic pharmaceutical companies have also initiated the development of new drugs for obesity treatment in similar therapeutic areas. In late October 2019, Glutazumab Injection, a recombinant anti-human GLP-1 receptor humanized monoclonal antibody injection developed by the domestic pharmaceutical company Hongyun Huaning, received approval for clinical trials, intended for use in clinical trials for adult overweight or obesity. Glutazumab has a half-life exceeding one week, and early clinical trials completed in Australia demonstrated favorable safety profiles, holding promise for development as a once-weekly weight-loss medication.