Introduction
Obesity, a complex and heterogeneous disease affecting billions worldwide, has become a global health crisis. Recognizing the urgent need for innovative and effective treatments, Roche is strategically expanding its portfolio in the cardiovascular, renal, and metabolic (CVRM) disease space, with a strong focus on obesity. This article delves into Roche's recent activities in the weight loss market, including collaborations, drug development, and strategic shifts in its pipeline.
Collaboration with Zealand Pharma: A Transformational Partnership
On March 12, 2025, Roche announced an exclusive collaboration and licensing agreement with Zealand Pharma, a significant step towards maximizing the value of petrelintide for individuals living with overweight and obesity. This partnership aims to co-develop and co-commercialize petrelintide, Zealand Pharma’s amylin analog, both as a standalone therapy and as a fixed-dose combination with Roche’s lead incretin asset, CT-388.
Terms of the Agreement
The agreement outlines a clear division of responsibilities and financial considerations. Roche and Zealand Pharma will co-commercialize petrelintide in the United States and Europe, while Roche will secure exclusive commercialization rights in the rest of the world. Roche will also manage commercial manufacturing and supply.
Financially, Zealand Pharma will receive upfront cash payments of USD 1.65 billion, which includes USD 1.4 billion upon closing and USD 250 million over the first two anniversaries of the collaboration. Additionally, Zealand Pharma is eligible for development milestones of USD 1.2 billion, primarily linked to the initiation of Phase 3 trials with petrelintide monotherapy, and sales-based milestones of USD 2.4 billion, potentially totaling USD 5.3 billion. Zealand Pharma will receive tiered double-digit royalties up to high teens % royalties on net sales in the rest of the world. Zealand Pharma will pay Roche USD 350 million, offsettable against milestone payments, for the petrelintide/CT-388 fixed-dose combination product or next-generation petrelintide combination products being pursued under the collaboration agreement. The closing of the transaction is subject to regulatory approvals and other customary closing conditions. The parties expect that the transaction will close in Q2 2025.
Petrelintide: A Promising Amylin Analog
Petrelintide is a long-acting amylin analog designed for once-weekly subcutaneous administration. Its chemical and physical stability allows for co-formulation and co-administration with other peptides. Amylin, co-secreted with insulin, plays a crucial role in reducing body weight by restoring sensitivity to the satiety hormone leptin, thus inducing a feeling of fullness faster. Clinical and preclinical data suggest that petrelintide could offer weight loss comparable to GLP-1 receptor agonists but with improved tolerability.
Read also: Weight Loss Guide Andalusia, AL
Currently, petrelintide is being evaluated in Phase 2b clinical trials. The ZUPREME-1 trial, initiated in December 2024 (ClinicalTrials.gov ID: NCT06662539), focuses on individuals with obesity/overweight without type 2 diabetes (T2D), while the ZUPREME-2 trial, expected to begin in the first half of 2025, will include participants with obesity/overweight and T2D.
CT-388: A Dual GLP-1/GIP Receptor Agonist
CT-388 is another key asset in Roche's obesity pipeline. It is a once-weekly subcutaneous injectable, dual GLP-1/GIP receptor agonist developed for treating obesity and type 2 diabetes. Its design minimizes receptor internalization and desensitization, potentially leading to prolonged pharmacological activity. CT-388 is also undergoing Phase 2b clinical trials in individuals with overweight/obesity, both with and without type 2 diabetes.
Strategic Rationale
The collaboration with Zealand Pharma aligns with Roche's vision to develop petrelintide as a foundational therapy for weight management. By combining petrelintide with Roche’s portfolio and diagnostics expertise in cardiovascular and metabolic diseases, the company aims to transform the standard of care and positively impact patients’ lives. Adam Steensberg, President and Chief Executive Officer of Zealand Pharma, emphasized that Roche is the ideal partner, sharing a vision for petrelintide's potential as a stand-alone therapy and in combination with other agents.
Obesity: A Global Health Challenge
Obesity is a significant health challenge with over 200 related comorbidities, including type 2 diabetes, cardiovascular diseases, fatty liver, and chronic kidney disease. These conditions place a substantial burden on healthcare systems worldwide. By 2035, it is estimated that over 4 billion people will be obese or overweight, representing nearly 50% of the global population.
Roche's Commitment to Innovation and Personalized Care
Roche's approach to addressing obesity extends beyond pharmaceutical interventions. The company is integrating its pharmaceutical and diagnostics divisions to reimagine cardiometabolic care, moving towards holistic, personalized, and long-term support, from early diagnosis and treatment to monitoring.
Read also: Beef jerky: A high-protein option for shedding pounds?
The Challenge of Sustained Weight Loss
Despite advancements in obesity treatment, sustained weight loss remains a significant challenge. Many treatments focus on short-term weight loss, but long-term maintenance is often difficult. The heterogeneity of obesity means that patients respond differently to treatments, necessitating a more tailored approach.
The Future of Holistic Obesity Care
Roche envisions a future where treatment is guided by biomarkers and artificial intelligence (AI)-based algorithms. Better diagnostic profiling and treatment stratification could help mitigate issues from the outset. Dr. Gesa Albert, Indication Lead for CVRM, envisions a future where biomarker panels, including markers of inflammation, metabolism, and hormonal regulation, guide treatment decisions.
Building the Tools for Tomorrow
Roche is investing in early research, such as proteomics, AI-based algorithm development, and decentralized testing, to address the unmet medical needs of people with cardiometabolic disorders along the entire patient journey. The aim is to offer high-throughput testing in hospitals while empowering people at home with digital tools for managing their long-term treatment.
A New Era of Cardiometabolic Care
The future of care for people with obesity and related comorbidities lies at the intersection of biology, technology, and human behavior. By combining the strengths of pharmaceuticals and diagnostics, Roche is working to build a system that effectively treats cardiometabolic diseases from the moment a patient presents, creating a holistic, personalized understanding of each patient’s unique situation.
Discontinuation of CT-173: A Strategic Portfolio Adjustment
Despite its commitment to the obesity market, Roche has made strategic decisions to streamline its pipeline. In a recent move, Roche discontinued CT-173, an investigational PYY analog acquired through the acquisition of Carmot Therapeutics. Teresa Graham, CEO of Roche Pharmaceuticals Division, explained that the molecule did not meet Roche's criteria for developability and competitiveness.
Read also: Inspiring Health Transformation
Rationale for Discontinuation
Although preclinical data presented in September 2024 showed that CT-173, when combined with CT-388, could break weight loss plateaus in mouse models, the overall assessment led to its termination. Graham insisted that the discontinuation of CT-173 has very little impact on the overall obesity portfolio, as it was a very early-stage program.
Continued Confidence in Obesity Portfolio
Roche remains confident in its obesity portfolio, particularly in its ability to address different subsegments of the obesity market. The company believes its pipeline is well-positioned to take advantage of the segmentation related to comorbidities and the amount of weight loss.
Financial Performance and Key Products
In its Q2 report, Roche revealed 15.504 billion Swiss Francs in earnings, representing an 8% year-on-year growth. Ocrevus, indicated for multiple sclerosis, was Roche’s best-selling product with around $2.18 billion in sales, up 10% year-on-year.
Amylin Analogs and the Weight Loss Market
The deal with Zealand Pharma gives Roche access to amylin analogs, a class of experimental drugs that Roche didn’t obtain when it acquired Carmot Therapeutics. Despite some doubts following Novo's setbacks with a combination treatment called CagriSema, amylin-stimulating drugs appear to help people with obesity lose weight and could add to other types of drugs when used in combination.
Other Pipeline Adjustments
In addition to CT-173, Roche has also discontinued several Phase 1 candidates, including three solid tumor assets, a bladder cancer trial, a USP1 inhibitor (RG6614), and an eye disease candidate (RG7921). These decisions reflect Roche's commitment to prioritizing resources towards the most promising and competitive assets in its pipeline.