Novo Nordisk Delivers Updates on Development of Semaglutide, CagriSema, Amycretin, and More

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Novo Nordisk offered the medical community a bevy of updates related to its pharmacologic pipeline for obesity management and cardiometabolic health during their Capital Markets Day presentations on March 07, 2024.

During the presentation of obesity updates, the company shed light on developments in the clinical programs for semaglutide 2.4 mg, cagrisema, monlunabant, and amycretin.

Semaglutide 2.4 mg:

A majority of the presentation delivered during Capital Markets Day focused on semaglutide 2.4 mg. Beyond calling attention to increased demand and need for education surrounding antiobesity medications, Novo Nordisk identified new data from the SELECT and STEP-HFpEF trials.

When using a broad composite endpoint, which included cardiovascular death, coronary revascularization, myocardial infarction, stroke, hospitalization for heart failure, hospitalization for UA, 5-point nephropathy, and diabetes, use of semaglutide 2.4 mg was associated with a 37% reduction in risk of the composite endpoint relative to placebo therapy, with a number needed to treat of 9 over a 4-year period. Additionally, a slide was dedicated to underlining the reduction in heart failure endpoints shown in pooled analyses of the trial, with benefit seen for time-to-event for hospitalization for heart failure (HR, 0.42; 95% CI, 0.26 to 0.67) and time-to-event for hospitalization for heart failure and CV death (HR, 0.61; 95% CI, 0.44 to 0.84).

Semaglutide 2.4 mg in OA:

During their presentation, Novo Nordisk highlighted a slide containing data from the STEP 9 trial. Conducted with the intent of evaluating the efficacy and safety of semaglutide 2.4 mg in patients with osteoarthritis, results from the trial provided evidence of clinically meaningful improvements in pain and physical function. Primary endpoint results from the trial favored semaglutide (41.7 vs 27.5), with an estimated treatment difference in WOMAC pain score of 14.1 (95% CI, -19.98 to -8.30) after 68 weeks. The slide also highlighted use was associated with a mean change in body weight of 13.7% after 68 weeks and the agent appeared to be well-tolerated.

Phase 3 CagriSema Program:

Novo Nordisk also offered further insight into its ongoing phase 32 program for cagrisema, a combination of cagrilinitide and semaglutide. Named the REDFINE program, it will feature 6 trials, 5 of which are highlighted below:

• REDEFINE 1: 3400-patient trial examining cagrisema against monotherapies and placebo over 68 weeks, with weight loss serving as the primary outcome of interest.
• REDEFINE 2: 1200-patient trial examining cagrisema against placebo over 68 weeks, with weight loss serving as the primary outcome of interest.
• REDEFINE 3: 7000-patient trial examining cagrisema, with 3-point major adverse cardiovascular events serving as the primary outcome of interest.
• REDEFINE 4: 800-patient trial examining cagrisema against tirzepatide over 72 weeks, with weight loss serving as the primary outcome of interest.
• REDEFINE 5: 330-patient trial conducted in East Asia examining cagrisema against semaglutide 2.4 mg over 68 weeks, with weight loss serving as the primary outcome of interest.

Monlunabant:

Formerly INV-202, monlunabant is an oral small molecule CB1R inverse agonist. At their Capital Markets Day, Novo Nordisk presented data from a phase 1 trial indicating use was safe and well-tolerated, with efficacy results pointing to a statistically significant mean weight loss of 3.5 kg (3.3%) compared to 0.6 kg (0.5%) with placebo at day 28. At the time of presentation, the agent is being examined in ongoing phase 2 trials for diabetic kidney disease and obesity.

Amycretin:

Novo Nordisk concluded the obesity care portion of its Capital Markets Day presentation by sharing an update related to its development program for amycretin in obesity. A GLP-1 and amylin receptor agonist, amycretin is being examined in an oral and subcutaneous form.

Novo Nordisk presented phase 1 data from the oral amycretin program demonstrating use was associated with a mean change in body weight of -13.1% at 12 weeks among a 16-patient cohort with a mean baseline body weight of 89 kg. The company noted the phase 1 trial of subcutaneous amycretin is still ongoing and completion is expected in 2025 and future development plans will be defined based on data from this trial.