Novo Nordisk’s plan to revitalize CagriSema after mixed results

DENMARK – Novo Nordisk has acknowledged that the first phase 3 trial results for CagriSema, a new obesity drug, were disappointing and difficult to interpret.

However, the company is determined to revitalize the program with a new plan. Chief Executive Lars Fruergaard Jørgensen shared in the company’s fourth-quarter results update, “We remain confident in its potent biology and look forward to further exploring its potential and to making it available to patients.”

The drug, CagriSema, combines Novo Nordisk’s popular weight-loss treatment, Wegovy, which contains the GLP-1 agonist semaglutide, with a dual amylin and calcitonin receptor agonist called cagrilintide.

The goal is for this combination to outperform Wegovy in terms of efficacy and help protect Novo Nordisk’s obesity market share against competition from Eli Lilly’s Zepbound (tirzepatide), which showed better weight loss results in a direct comparison.

However, the initial phase 3 trial, REDEFINE 1, did not meet expectations. In the trial, patients experienced a 22.7% reduction in weight after 68 weeks, which was below the 25% target set by Novo Nordisk and similar to results seen with Zepbound.

Martin Holst Lange, the head of development at Novo Nordisk, explained that one possible reason for the results was a flexible treatment approach that allowed patients to reduce their dosage if they experienced side effects such as gastrointestinal discomfort.

Unfortunately, only around 57% of participants reached the maximum dose. On the positive side, the incidence of patients dropping out due to side effects was lower than in previous Wegovy trials—around 3.6% with CagriSema compared to 4.5% with Wegovy—indicating that there isn’t a significant toxicity issue with the drug.

Lange pointed out that among the patients who did reach the higher dose, weight loss had not plateaued by the 68-week mark, which suggests there could be potential for even more weight loss if the trial continues for a longer period.

The company’s next step is to start a new trial, REDEFINE 11, which will focus on a personalized approach to dosing.

This approach will allow patients to increase their dosage again if side effects resolve, a strategy Novo Nordisk believes could improve CagriSema’s efficacy while maintaining a good safety profile. The new trial is set to begin in the first half of this year.

In addition, Novo Nordisk is eagerly awaiting results from the REDEFINE 2 trial, which is expected to be completed by the end of the first quarter.

The company is also working on other weight-loss treatments, including high-dose versions of Wegovy and an oral version of semaglutide called Rybelsus, as well as oral amycretin, which is currently in phase 1/2 testing.