What went wrong with Novo Nordisk’s CagriSema obesity drug trial

On December 20, Danish pharmaceutical giant Novo Nordisk saw a dramatic $125 billion drop in market value following disappointing results from a late-stage trial of its experimental obesity drug, CagriSema. The drug helped patients reduce their weight by only 22.7%, falling short of the anticipated 25% weight loss. As a result, Novo’s shares plummeted by as much as 27%, reaching their lowest point since August 2023.

Novo stated that when patients adhered to the CagriSema treatment, they achieved an average weight loss of 22.7% after 68 weeks, with 40.4% losing 25% or more. However, this was still below the company’s target. In addition to the underwhelming overall results, investors and analysts were puzzled by another piece of data based on which rumours spread: only 57% of patients in the trial were on the highest dose of the drug by the end of the 68-week trial period.

And this raised the question of whether a section of patients had faced tolerability issues, suffered side effects, and had to limit their intake.

What is CagriSema?

Designed to address obesity and type 2 diabetes, CagriSema is a combination therapy of cagrilintide and semaglutide, which should be injected subcutaneously once a week. 

Cagrilintide mimics the action of amylin, a hormone that promotes feelings of fullness after meals, thus reducing food intake. Meanwhile, semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA), a class of drugs that mimic the actions of the hormone GLP-1, which increases insulin secretion, suppresses glucagon release, and slows gastric emptying, contributing to better blood sugar control.

The phase three trial for CagriSema involved around 3,400 participants with obesity or those who were overweight with one or more comorbidities and lasted for 68 weeks. The study followed a flexible protocol, enabling patients to adjust their dosage throughout. 

By the trial’s conclusion, just 57.3% of those on CagriSema reached the highest dose. In contrast, significantly higher percentages of patients in two other groups—those who received either cagrilintide or semaglutide alone—achieved the highest dose: 83% for cagrilintide and 70% for semaglutide.

While talking to THE WEEK, an expert diabetologist from India, who preferred to remain anonymous, explained that drugs in the semaglutide category typically induce side effects such as nausea, vomiting, and anorexia. "For some patients, it becomes intolerable," he said.

Rising drug war

Novo Nordisk and American firm Eli Lilly currently dominate the obesity treatment market with their respective GLP-1 drugs. However, US-based financial services firm Morningstar predicts that in the coming years, numerous challengers may emerge with competing treatments, beginning to capture a significant portion of the, albeit massive, market.

According to a Morningstar report, 16 new obesity drugs could be launched by 2029, with these new contenders expected to account for approximately USD 70 billion of the GLP-1 market by 2031. By that time, the entire GLP-1 analog market is projected to reach USD 200 billion, with 68% of that revenue anticipated to come from the treatment of overweight and obesity.

Notably, when Novo Nordisk’s shares plunged after disappointing trial results, shares of Eli Lilly jumped more than 5% in early trading on December 20.