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Development of Cagrilintide, a Long-Acting Amylin Analogue. 2021
Thomas Kruse, and
Jakob Lerche Hansen, and
Kirsten Dahl, and
Lauge Schäffer, and
Ulrich Sensfuss, and
Christian Poulsen, and
Morten Schlein, and
Ann Maria Kruse Hansen, and
Claus Bekker Jeppesen, and
Charlotta Dornonville de la Cour, and
Trine Ryberg Clausen, and
Eva Johansson, and
Simone Fulle, and
Rikke Bjerring Skyggebjerg, and
Kirsten Raun
Novo Nordisk, Novo Nordisk Park, DK-2760 Maaloev, Denmark.
A hallmark of the pancreatic hormone amylin is its high propensity toward the formation of amyloid fibrils, which makes it a challenging drug design effort. The amylin analogue pramlintide is commercially available for diabetes treatment as an adjunct to insulin therapy but requires three daily injections due to its short half-life. We report here the development of the stable, lipidated long-acting amylin analogue cagrilintide (23) and some of the structure-activity efforts that led to the selection of this analogue for clinical development with obesity as an indication. Cagrilintide is currently in clinical trial and has induced significant weight loss when dosed alone or in combination with the GLP-1 analogue semaglutide.
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