Novo Nordisk Overhauls Pipeline Amid Leadership Changes and Market Challenges

Novo Nordisk, the Danish pharmaceutical giant, has announced a significant restructuring of its drug pipeline, coinciding with leadership changes and disappointing sales figures for its flagship obesity and diabetes medications. The company has discontinued several high-profile drug candidates, signaling a shift in its research and development strategy.

Major Pipeline Clearout

Novo Nordisk has abandoned two obesity drugs as part of a broader pipeline review. The company has halted development of NNC0519-0130, a once-weekly GLP-1/GIP co-agonist, despite positive phase 2 results showing statistically significant weight loss compared to placebo after 36 weeks. The decision was attributed to "portfolio considerations," suggesting a strategic realignment of the company's research priorities.

Additionally, Novo Nordisk has discontinued INV-347, a next-generation CB1 receptor blocker acquired through its buyout of Inversago in 2023. While a phase 1 study completed in May demonstrated that the oral small molecule was "safe and well tolerated" in patients with normal weight and obesity, the company cited its "pharmacokinetic profile and portfolio considerations" as reasons for termination.

Setbacks in Liver Disease and Metabolic Disorders

The pipeline overhaul extends beyond obesity treatments. Zalfermin, a long-acting FGF21 analogue, failed to improve liver fibrosis when combined with semaglutide in a phase 2 trial of approximately 700 patients with metabolic dysfunction-associated steatohepatitis (MASH). Consequently, Novo Nordisk has ended zalfermin's development for fatty liver disease, though a phase 1 study for type 1 diabetes is ongoing to inform potential future candidates.

Furthermore, the company has halted development of ANGPTL3i, a monoclonal antibody targeting dyslipidaemia. Despite demonstrating safety and tolerability in phase 1, the drug fell victim to the company's portfolio reassessment.

Corporate Restructuring and Market Challenges

The extensive pipeline review comes amid significant changes in Novo Nordisk's leadership. CEO Lars Fruergaard Jørgensen and Chief Scientific Officer Marcus Schindler, Ph.D., are departing the company. These exits are set against a backdrop of reduced U.S. sales for semaglutide, marketed as Wegovy for obesity and Ozempic and Rybelsus for diabetes.

Despite these challenges, Novo Nordisk is not abandoning its obesity research. The company's recent $200 million acquisition of Septerna has added a preclinical GLP-1/GIP/Glucagon triple agonist and two oral molecules for obesity to its early-stage pipeline, potentially filling gaps left by discontinued programs.

As Novo Nordisk navigates this period of transition, the pharmaceutical industry watches closely to see how these strategic decisions will shape the company's future in the competitive markets of obesity and diabetes treatment.