The race to lead the market for pharmacological treatments for obesity This adds another bitter chapter for Novo Nordisk. The Danish company has acknowledged that its experimental combination CagriSema, poised to be one of their major weight management releases, It has not managed to match the results of tirzepatide, Eli Lilly's star active ingredient, in a head-to-head comparative trial.
The late-stage, long-term follow-up study confirms that advantage in efficacy of tirzepatide It remains, at least with the currently evaluated doses of CagriSema. This outcome has had an immediate impact on financial markets, with a Novo Nordisk shares sharply corrected, and reinforces the perception that Lilly remains a step ahead in one of the most competitive segments of the pharmaceutical sector.
Key results from the Redefine 4 trial
The open-label phase 3 trial Redefine 4 directly compared CagriSema (cagrilintide 2,4 mg + semaglutide 2,4 mg fixed dose) with tirzepatide 15 mg, active ingredient marketed by Eli Lilly under the brands Mounjaro y ZepboundThe study included 809 people with obesity and at least one comorbidity, with an average starting weight of around 114,2 kg, treated for 84 weeks with weekly subcutaneous injections.
According to data reported by Novo Nordisk, the participants who received CagriSema 2,4 mg/2,4 mg they reached a average weight loss of 23% at the end of the follow-up period. In the group treated with tirzepatide 15 mg The weight reduction was located at the 25,5%This represents a noticeable difference in a context of almost millimeter-level competition for every percentage point of efficiency.
When data is analyzed using the so-called estimation of the treatment regimen, which attempts to approach the effect under ideal adherence to the drug, the gap remains: the CagriSema group obtained a 20,2% weight loss, in front of 23,6% observed with tirzepatide. On this basis, Novo Nordisk has admitted that The trial did not meet the primary criterion of demonstrating the non-inferiority of CagriSema regarding tirzepatide after 84 weeks.
A relevant element of the design is that it was a open trialIn other words, both the researchers and the participants knew beforehand which of the two treatments they were receiving. While this type of design can simplify study logistics, it also introduces potential behavioral and evaluation biases, something the company itself has hinted at by describing some aspects of the results as “anomalous” compared to previous data for tirzepatide.
Safety profile and role of the GLP-1 + amylin combination
Despite lagging behind in absolute weight loss, Novo Nordisk wanted to emphasize that CagriSema showed a favorable safety and tolerability profile during the trial. The drug combines two mechanisms: the semaglutide, a GLP-1 receptor agonist already widely known in Europe for its use in obesity and diabetes, and the cagrilintida, an amylin analogue designed to complement that action and enhance the effect on appetite and metabolism.
The company insists that this dual approach could turn CagriSema into the first treatment that combines GLP-1 and amylin Specifically targeted at obesity once approved, this would open the door to more flexible therapeutic approaches, especially in patients who do not respond well to GLP-1 biologics as monotherapy. From a clinical perspective, the possibility of modulating different hormonal axes continues to generate interest among endocrinologists and obesity units in hospitals both in Spain as in the rest of Europe.
In the words of Novo Nordisk's scientific management, the results reinforce the idea that Cagrilintide “adds” weight loss effects to the already known benefits of semaglutide, although so far this additional benefit has not been enough to outperform tirzepatide in a head-to-head comparison. The company maintains that, in light of the studies already completed, there is still room to explore the full potential of this combination, especially through higher doses of CagriSema and different test designs.
In addition to the efficacy component, the pharmaceutical company points out that factors such as gastrointestinal tolerabilityEase of use and continuity of treatment in real life will be key when clinicians and European health systems decide which molecules to prioritize in their protocols, something especially sensitive in countries with strong budgetary pressures like Spain.
Market reaction and competitive pressure against Eli Lilly
Investor reception was less than forgiving. Following the release of the Redefine 4 data, the Novo Nordisk shares Shares plummeted by around 15% on the Copenhagen stock exchange. The market interpretation was clear: the candidate tasked with reinforcing the company's leadership in the obesity market is not only failing to widen the gap, but is actually ceding more ground to its main rival.
In parallel, the Eli Lilly shares They reacted in opposite ways, with Gains of nearly 4% in pre-market trading in the United States. Investors interpret these results as consolidating tirzepatide's position as a leading treatment within the new wave of injectable weight-loss drugs, a market that already moves tens of billions of euros annually and is expected to continue growing strongly in Europe.
From Novo Nordisk, senior executives such as the executive vice president of R&D, Martin Holst Langeand the deputy CEO, Mike DoustdarThey have attempted to qualify the most negative interpretation. Doustdar even pointed out to analysts that the study presents an "anomaly" with respect to the expected behavior of tirzepatide, comparing it with the data from the product information sheet and previous trials, and insisted that they continue to maintain “High expectations” regarding CagriSema as part of the long-term strategy on obesity.
The company also notes that it is under a strong pressure on production capacity to meet the demand for its already marketed treatments, such as semaglutide for obesity, and that the competitive landscape has become more challenging with the entry of compounding companies and other players trying to gain market share in this segment. In addition, price negotiation with health authorities —including those of the European Union— and the budgetary constraints that condition the pace of adoption in public systems such as the Spanish one.
Regulatory application and next steps for CagriSema
Beyond the comparative setback, Novo Nordisk is not currently altering its regulatory roadmap. The pharmaceutical company has already submitted a application for approval to the US FDA for the use of CagriSema as a weight management treatment, relying primarily on pivotal trials Redefine 1 y Redefine 2The agency's decision is expected by 2026 lateAnd the company insists that the result of Redefine 4 is not the central pillar on which the future technical specifications will be evaluated.
Meanwhile, Novo Nordisk is preparing for the Start of a new phase 3 trial with higher doses of CagriSemawhich would be launched in the second half of the year. The objective is to determine whether an upward adjustment in dosage can close part of the efficacy gap compared to tirzepatide, while maintaining an acceptable safety profile. Other studies are also underway within the program. Redefines, entre ellos Redefine 11, intended to better characterize the place that the combination could occupy in the therapeutic arsenal.
With regard to Europe and Spain, the regulatory timetable will depend largely on the initial evaluation by the FDA and the European Medicines Agency (EMA)as well as subsequent public funding decisions. In the current context, with healthcare systems debating the extent to which they should fund high-cost therapies for a disease as prevalent as obesity, the relationship between efficacy, safety, and price will be crucial for CagriSema's inclusion in clinical guidelines and real-world practice.
In summary, the data from Redefine 4 confirms that CagriSema fails to outperform tirzepatide in weight loss In a head-to-head trial, this represents a setback for Novo Nordisk's aspirations in one of the industry's most dynamic markets. Even so, the company remains committed to this GLP-1 + amylin combination, while European investors and healthcare systems closely monitor a competition that, beyond stock market figures, will significantly impact the therapeutic options for millions of people with obesity in the coming years.
