Novo Nordisk is anticipated to release Phase III data for CagriSema, a next-generation weight loss treatment combining semaglutide, a GLP-1 receptor agonist, with cagrilintide, a long-acting amylin analog. Analysts suggest this combination could mark a significant advancement in obesity management.
CagriSema: Combining GLP-1 and Amylin Pathways
CagriSema leverages the mechanisms of both semaglutide and cagrilintide. Semaglutide, known as Ozempic for type 2 diabetes and Wegovy for obesity, is combined with cagrilintide, which mimics amylin, a pancreatic peptide that reduces blood glucose levels and slows gastric emptying. Leerink Partners analysts highlight amylin's role in promoting satiety and affecting the hedonic aspects of eating by acting on brain regions to reduce reward feelings after eating.
In a Phase II trial, CagriSema demonstrated a 15.6% reduction in body weight, compared to 5.1% with semaglutide alone and 8.1% with cagrilintide alone. The combination also led to a greater reduction in HbA1c levels. Novo Nordisk has initiated Phase III trials, including REDEFINE 1 for weight loss and REDEFINE 2 for type 2 diabetes patients with excess weight. REDEFINE 1 data is expected by the end of the year, with REDEFINE 2 data anticipated in the first half of 2025. CagriSema is also being evaluated in a head-to-head study against Eli Lilly’s tirzepatide.
Advantages of Amylin Mimetics
Amylin mimetics may offer advantages over GLP-1 therapies, potentially leading to better weight reduction quality with less lean mass loss relative to fat. They may also be more effective in type 2 diabetes patients due to insulin sensitization effects and potentially more tolerable than GLP-1 agonists. However, cagrilintide cannot be co-dissolved with semaglutide, requiring a dual-chamber injection device for commercialization.
Other Amylin-Based Therapies in Development
Eli Lilly is also developing amylin-based therapies, including eloralintide, a weekly therapy being tested with tirzepatide in obese individuals. Phase II study results are expected in mid-2025. Lilly is also conducting other trials combining eloralintide with tirzepatide in obese and overweight type 2 diabetes patients. They are exploring the potential of co-formulating eloralintide with tirzepatide or retatrutide, although current trials administer the drugs separately.
Zealand Pharma is advancing petrelintide, a long-acting amylin analog. Phase Ib study data showed an average weight reduction of 8.6% at 16 weeks, compared to 1.7% in the placebo group. Zealand Pharma highlights petrelintide's chemical and physical stability, making it a potential candidate for combination with other therapeutic peptides. A mid-stage study for petrelintide is expected to begin imminently, with data anticipated by the end of 2025 or early 2026.
AstraZeneca is developing AZD6234 as a potential alternative or complement to GLP-1 therapies. Early-stage data presented at ObesityWeek 2024 showed an encouraging safety profile and promising weight loss, though detailed data remain limited.
