Novo Nordisk Revisits CagriSema Data, Emphasizes Individualized Treatment Approach

Novo Nordisk executives are working to rebuild investor confidence in their obesity candidate CagriSema, following a disappointing Phase III readout that caused a significant drop in the company's market value. During a recent fourth-quarter earnings call, the pharmaceutical giant presented a new analysis of the REDEFINE 1 trial data, suggesting that personalized treatment regimens could enhance the drug's efficacy.

CagriSema's Performance and New Analysis

CagriSema, a combination of semaglutide (the active ingredient in Wegovy and Ozempic) and cagrilintide, initially failed to meet Novo Nordisk's ambitious 25% weight loss target in late 2024. The drug achieved a 22.8% weight reduction after 68 weeks, falling short of expectations and resulting in a $72 billion market cap loss for the company.

Executive Vice President of Development Martin Holst Lange presented a post-hoc analysis of the REDEFINE 1 trial, dividing participants into subgroups based on dosage:

• 57% of participants on the highest dose (2.4 mg) achieved 22.2% mean weight loss at 68 weeks, with potential for further reduction.
• 29% of participants on the lowest doses (average 1.1 mg) reached 25.1% mean weight loss at 68 weeks, surpassing the original target.

Lange emphasized that these findings suggest a patient-centric approach, considering factors such as initial dose escalation, dose re-escalation, and trial duration, could potentially enhance CagriSema's efficacy while maintaining a favorable safety profile.

Implications for Future Development and Competition

Novo Nordisk is moving forward with additional trials to further explore CagriSema's potential:

1. REDEFINE 11: A Phase III trial examining longer duration, dose escalation, and dose re-escalation.
2. REDEFINE 4: A head-to-head trial against Eli Lilly's tirzepatide (Zepbound), set to read out in the second half of 2025.

CEO Lars Fruergaard Jørgensen addressed concerns about the complex dosing requirements, stating that physicians are accustomed to patients responding differently to treatments. He attributed the pronounced differences in response to CagriSema's potency.

While Novo Nordisk executives remain optimistic about CagriSema's potential, they are cautious about setting specific targets for the upcoming REDEFINE 4 trial. Lange stated, "I think it's too early to speculate, but we will see the data when we see them," indicating a more measured approach following the previous setback.