Cagrilintide

Novo Nordisk’s amylin combination shot amycretin allowed patients with diabetes to lose up to 14.5% of their body weight in just over eight months. Patients in the same mid-stage trial who were given a pill form of the drug lost up to 10.1% of their weight at the same time point. Novo said Tuesday that these weight-loss figures are statistically significant compared with injected and oral placebos, which yielded weight loss of 2.6% and 2.5%, respectively. The pharma company is planning to start an “extensive” Phase 3 program for amycretin in “multiple indications” next year. The drug could one day generate considerable sales for Novo, with 2032 sales forecasts in excess of $4 billion, according to Evaluate Pharma. Novo’s stock ticked up as much as 4% on the Copenhagen exchange Tuesday, a day after it took a hit when its gamble on GLP-1 for Alzheimer’s disease failed to pay off . In the Phase 2 trial, patients given Novo’s drug also had better blood glucose control than the placebo subjects. Those on injected amycretin had their glycated hemoglobin levels reduced by up to 1.8% by the end of the study; those taking the pill form had reductions of up to 1.5%. The respective decreases with the injected and oral placebos were 0.2% and 0.4%. Up to 89.1% of those given the shot achieved glycated hemoglobin levels below 7%, which is generally considered a good target for most diabetes patients. Among patients given the oral form, 77.6% hit this goal. The estimated improvements in blood sugar were all statistically significant versus placebo, Novo said, meaning the trial hit its primary endpoints. Novo did not give details on the specific dose levels that produced the results on weight loss and blood sugar. The trial’s dosing scheme called for six dose levels of the injected form, with patients in the highest dose cohort receiving once-weekly shots titrated up to 40 mg per week. These patients maintained the 40 mg dose for four weeks, Novo said. Of the subjects given the pills, the high-dose cohort received 50 mg per day. The Phase 2 trial is the first for amycretin in type 2 diabetes. It enrolled 448 patients who were not well controlled on standard care, consisting of metformin with or without an SGLT2 inhibitor. Both forms of amycretin appeared safe and well-tolerated, Novo said , with the most common side effects being gastrointestinal, the “vast majority” of which were mild to moderate. Amycretin is a single molecule that activates the receptors of both GLP-1 and amylin. It differs from Novo’s higher-profile drug CagriSema, which is a two-drug combo of the amylin analog cagrilintide and the GLP-1 agonist semaglutide. Amycretin has already proven itself effective in obesity. In a Phase 1/2 study in that condition, patients given injected amycretin lost 22% of their body weight at about eight months. In a Phase 1 trial of the oral form of amycretin in overweight or obese patients, those given two 50 mg amycretin pills a day had a 13.1% drop in body weight at three months. CagriSema is in a suite of Phase 3 trials in patients with diabetes but not obesity, though none have yet reported data. In a late-stage study in patients with both conditions, CagriSema resulted in a 15.7% weight loss. Of the two drugs, CagriSema is projected to be the more lucrative — its 2032 sales forecasts stand at around $25 billion.