Novo Nordisk A/S (NVO  ) stock is plunging on Monday on disappointing headline data from its REDEFINE 4, an open-label phase 3 trial from the global REDEFINE clinical trial program. After the update, Novo Nordisk stock hit its 52-week low. Over the year, the stock has fallen around 48%, according to Benzinga Pro data.

The 809-subject REDEFINE 4 was an 84-week trial investigating CagriSema (a fixed dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg) compared to tirzepatide 15 mg, both administered once weekly and subcutaneously.

Eli Lilly and Co.'s (LLY  ) tirzepatide is marketed under the Zepbound and Mounjaro brands.

Efficacy Results: CagriSema vs. Tirzepatide

When evaluating the effects of treatment, if all people adhered to treatment, people treated with CagriSema 2.4 mg/2.4 mg achieved a weight loss of 23.0% after 84 weeks, compared to 25.5% with tirzepatide 15 mg.

When applying the treatment regimen estimand, people treated with CagriSema 2.4 mg/2.4 mg achieved a weight loss of 20.2% compared to 23.6% with tirzepatide at 84 weeks.

The trial did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared to tirzepatide after 84 weeks.

In the trial, CagriSema appeared to have a safe and well-tolerated profile. The most common adverse events with CagriSema were gastrointestinal, and the vast majority were mild to moderate and diminished over time, consistent with the GLP-1 receptor agonist class.

Management Commentary

"Based on the learnings from completed studies, we look forward to the REDEFINE 11 readout and the initiation of the higher-dose CagriSema trial, which are both designed to assess the full weight-loss potential of CagriSema", said Martin Holst Lange, executive vice president, R&D and chief scientific officer at Novo Nordisk.

CagriSema for weight management was submitted to the U.S. Food and Drug Administration (FDA) in December 2025 based on the REDEFINE 1 and REDEFINE 2 pivotal trials, and an FDA decision is anticipated by late 2026.

The REDEFINE 11 phase 3 trial exploring CagriSema 2.4/2.4 mg full weight-loss potential in obesity is expected to report data during the first half of 2027, while initiation of the phase 3 CagriSema higher-dose trial is planned for the second half of 2026.

In February, Novo Nordisk shared headline results from the REIMAGINE 2 phase 3 trial of CagriSema, demonstrating higher HbA1c reduction and weight loss at week 68 versus semaglutide, across all tested doses in the trial.

NVO Price Action: Novo Nordisk shares were down 13.29% at $41.12 during premarket trading on Monday. The stock is trading at a new 52-week low, according to Benzinga Pro data.