Novo Nordisk falls as CagriSema obesity data shows no clear edge vs Zepbound

Investing.com -- Novo Nordisk A/S (CSE:NOVOb) shares fell over 2% on Monday after full Phase III data for its obesity drug CagriSema, presented at the American Diabetes Association (ADA) Scientific Sessions in Chicago, failed to show clear advantages over Eli Lilly’s Tirzepatide (Zepbound).

CagriSema, a combination of cagrilintide and semaglutide (Wegovy), showed approximately 20% weight loss at week 68 in the REDEFINE-1 trial, similar to Tirzepatide’s 20-21% at week 72.

Novo Nordisk flagged stronger outcomes for “fast responders,” with about 25% weight loss, but comparable rapid responses have been reported with Tirzepatide (31%) and semaglutide monotherapy (27%) in the SURMOUNT-5 trial, Jefferies said.

Gastrointestinal (GI) tolerability remains a concern for CagriSema. Nausea occurred in 55% of patients, compared with 31-33% for Tirzepatide. 

Vomiting was reported in 26% of CagriSema users versus 11-12% for Tirzepatide. Constipation and diarrhea rates were also higher with CagriSema at 31% and 25%, respectively, compared with 12-17% and 21-23% for Tirzepatide, according to Jefferies. 

These adverse events limited the proportion of patients achieving the maximum dose, with only 57.3% reaching the highest dose, compared to 70-83% for cagrilintide or semaglutide monotherapy, Jefferies noted.

Body composition results also failed to support earlier hypotheses that CagriSema’s amylin component would promote greater fat mass reduction relative to lean mass. 

DEXA scans showed that approximately two-thirds of the weight loss was from fat mass, while about half was from lean mass reduction, similar to Wegovy, according to J.P. Morgan.

Separately, Novo Nordisk presented early data for its oral amycretin program. In Phase I and Ib/IIa trials, amycretin achieved 23% placebo-adjusted weight loss at 36 weeks for the 20mg dose, J.P. Morgan added. 

However, tolerability remains an issue, with nausea occurring in 79% of patients on amycretin compared to 40% for placebo. 

The high placebo-adjusted rates make it difficult to interpret overall tolerability, J.P. Morgan and William Blair noted.

Analysts see limited clinical differentiation for CagriSema relative to Zepbound, as Tirzepatide continues to gain commercial momentum. 

Adding to the commercial headwinds, injection site reactions were more frequent with CagriSema at 12% in REDEFINE-1, compared to 2.6% for Wegovy and 3.0% for placebo, according to William Blair.

Despite the challenges, Novo Nordisk plans to submit CagriSema for regulatory approval in obesity in the first quarter of 2026.