Pivotal Trial Data Unveiled
Novo Nordisk has reported new late-stage trial data for its investigational amylin analogue cagrilintide, showing weight loss results that fell below those seen with its already approved obesity treatment Wegovy. Despite this, the company confirmed plans to move forward with further clinical development.
The data, unveiled at the European Association for the Study of Diabetes (EASD) congress in Vienna, came from a sub-analysis of the Phase III REDEFINE 1 trial. Cagrilintide, administered once weekly at a 2.4-mg dose, achieved an average weight loss of 11.8% over 68 weeks in nondiabetic patients with obesity or who were overweight. This compared to 2.3% in the placebo cohort.
Comparative Efficacy and Tolerability
For comparison, Wegovy, Novo’s GLP-1 therapy, delivered 14.9% weight loss in the Step-1 trial of a similar patient group over the same duration. In addition, the still-unapproved oral version of Wegovy, tested in the Oasis 1 study, achieved 15% weight reduction at 68 weeks.
Novo described cagrilintide as “well tolerated,” with 1% of patients discontinuing treatment due to nausea, versus 0.1% in the placebo group. In Wegovy’s Step-1 trial, 4.5% of patients discontinued treatment due to gastrointestinal events, compared to 0.8% for placebo.
Combination Therapy and Expert Insights
Cagrilintide is a dual amylin receptor and calcitonin receptor agonist (DACRA), and analysts have suggested DACRAs have the potential for a more tolerable safety profile than GLP-1s. While the current data assessed the drug as a monotherapy, Novo has also tested cagrilintide in combination with semaglutide, the active ingredient in Wegovy, under the name CagriSema. A Phase III readout last year showed 22.7% weight loss with CagriSema, short of the company’s expectations of at least 25%. Another trial in March reported 15.7% weight loss in Type 2 diabetes patients.
“These data highlight the exciting potential of cagrilintide to offer an alternative approach for people to lose weight, achieve health-related outcomes and manage their obesity, including a favorable tolerability profile,” said Timothy Garvey, M.D., lead investigator and director of the Diabetes Research Center at the University of Alabama at Birmingham. He added that multiple options are needed to address the varying responses of patients to obesity treatments.
Future Developments and Market Reaction
Novo Nordisk confirmed plans to launch a dedicated Phase III program for cagrilintide, named RENEW, in the fourth quarter of this year. Martin Holst Lange, M.D., Ph.D., Novo’s chief scientific officer, stated that in clinical trials cagrilintide has provided “substantial weight loss, in a distinct manner compared to approved obesity medications, and appears well-tolerated.” He said the company looks forward to further investigating the therapy’s potential in the upcoming trial.
The presentation of cagrilintide’s late-stage data marks the first time the drug has been showcased as a standalone therapy. The trial involved 3,417 adults with one or more obesity-related comorbidities. Novo’s stock price rose by 3% to $57.30 following the announcement, up from a closing price of $55, though the company’s stock has lost a third of its value so far this year against a backdrop of disappointing obesity drug sales, a leadership shake-up, and significant layoffs.
Meanwhile, competition in the obesity drug space continues, with Eli Lilly advancing its own amylin candidate and oral GLP-1 orforglipron, which is also being presented at the EASD congress.
