Novo Nordisk has abandoned another GLP-1/GIP co-agonist and CB1 receptor as part of a significant pipeline clearout that coincides with disappointing obesity sales and a leadership shake-up.
The Danish pharma completed a phase 2 study of the GLP-1/GIP co-agonist analog, dubbed NNC0519-0130, in patients who are overweight or with obesity in June. That study hit its primary objective of demonstrating statistically significant weight loss compared with placebo across all doses after 36 weeks, Novo revealed in its second-quarter earnings release.
Despite the positive readout, the company said this morning that, due to “portfolio considerations,” it has decided not to take this weight management program further.
NNC0519-0130 was Novo’s attempt to develop a once-weekly GLP-1/GIP co-agonist, after executives jettisoned a once-monthly GLP-1/GIP candidate a year ago over a “current profile [that] was not something that we would take into further clinical development.”
One new addition to Novo’s pipeline that could potentially plug this gap is a preclinical GLP-1/GIP/glucagon triple agonist acquired as part of the pharma’s $200 million licensing agreement with Septerna in May. That deal also brought Novo two oral molecules for obesity in preclinical development.
But, until those drugs make it into human trials, Novo’s clinical pipeline is going to seem emptier—especially because NNC0519-0130 wasn’t the only obesity drug the company jettisoned today.
The drugmaker also revealed that it has given up on INV-347, a next-generation CB1 receptor blocker acquired as part of the buyout of Inversago in 2023. CB1 receptor blockade is an old idea—Sanofi won approval for a drug with the mechanism in 2006—but Novo identified Inversago as a company capable of realizing the potential of the approach.
The more advanced asset from that deal, called monlunabant, already flopped in a phase 2 diabetic kidney disease trial in February. To make matters worse, Novo reported some mild to moderate neuropsychiatric side effects, which brought back memories of European authorities’ withdrawal of approval for Sanofi’s CB1 obesity drug back in 2009 after studies found it doubled the risk of psychiatric disorders.
However, neurological effects didn’t seem to be behind Novo’s decision to drop INV-347. The pharma said this morning that it had completed a phase 1 study in May of patients with both normal weight and obesity that showed the oral small molecule to be “safe and well tolerated.”
Instead, the company has given up on the asset due to its “pharmacokinetic profile and portfolio considerations.”
Beyond obesity, Novo also revealed this morning that its broader pipeline has suffered its own setbacks. A phase 2 trial of zalfermin, a long-acting FGF21 analog, failed to improve liver fibrosis when given in combination with Novo’s own semaglutide in a phase 2 trial of about 700 patients with metabolic dysfunction-associated steatohepatitis.
This led Novo to end development of zalfermin for the fatty liver disease.
The company hasn’t completely given up on the therapy, having kicked off a phase 1 study in July for Type 1 diabetes. However, the company explained that the purpose of this trial is “to generate data to inform potential future first human dose candidates rather than progress into next stage development phases.”
The final drug that had its future cut short is ANGPTL3i, a monoclonal antibody Novo had been developing for the metabolic disorder dyslipidemia. A phase 1 study of the drug showed it was safe and well tolerated, but this wasn’t enough to save it from becoming another victim of the company’s “portfolio considerations.”
Assessing these various pipeline changes, Jefferies analysts said in a note this morning that it remains to be seen whether the “larger R&D clean-out than usual ... reflects a strategic re-assessment or just coincidence.”
The pipeline overhaul reflects a significant restructure at the top of the company, with both CEO Lars Fruergaard Jørgensen and Chief Scientific Officer Marcus Schindler, Ph.D., departing against a backdrop of reduced sales for semaglutide—sold as Wegovy for obesity and Ozempic and Rybelsus for diabetes—in the U.S.