Novo Nordisk’s injectable amylin alternative to Wegovy appears to have underperformed the approved obesity blockbuster in a phase 3 readout, but the pharma is still planning to push ahead with development.
The data unveiled this morning demonstrate the performance of a 2.4-mg weekly dose of cagrilintide, a long-acting amylin analogue, which was given to nondiabetic patients with obesity or who are overweight. Over 68 weeks, cagrilintide was tied to average weight loss of 11.8%, compared to 2.3% for the placebo cohort.
The data come from a sub-analysis of the Redefine 1 trial and were presented at the European Association for the Study of Diabetes congress in Vienna.
While trial-to-trial comparisons are difficult for several reasons, Novo’s approved GLP-1 weight loss drug Wegovy achieved 14.9% average weight reduction in Step-1, a 68-week clinical trial of nondiabetic patients with obesity or who are overweight and have at least one weight-related comorbidity. Another study called Oasis 1 showed 15% weight loss after 68 weeks of treatment with the oral version of Wegovy, which is still under FDA review.
When it came to the safety of Novo's investigational asset, the Danish pharma giant said the drug was “well tolerated,” with 1% of patients on cagrilintide discontinuing their treatment due to nausea compared to 0.1% in the placebo cohort.
Cagrilintide functions as a dual amylin receptor and calcitonin receptor agonist (DACRA), and analysts have suggested DACRAs have the potential for a more tolerable safety profile than GLP-1s.
This is compared to Step-1, in which 4.5% of patients receiving Wegovy and 0.8% on placebo discontinued treatment due to gastrointestinal events.
While today’s data are from the use of cagrilintide as a monotherapy, Novo has already been evaluating the amylin analogue combined with Wegovy’s ingredient semaglutide as a therapy called CagriSema. A phase 3 readout for CagriSema at the end of last year crashed the company’s stock price after the 22.7% weight loss result, seen at 68 weeks, came in below the pharma’s expectations of 25% or more.
A second trial in March, this time among patients with Type 2 diabetes, demonstrated 15.7% weight loss for CagriSema at the 68-week mark and only served to embed the disappointment.
“These data highlight the exciting potential of cagrilintide to offer an alternative approach for people to lose weight, achieve health-related outcomes and manage their obesity, including a favorable tolerability profile,” lead investigator Timothy Garvey, M.D., study investigator and director of the Diabetes Research Center at the University of Alabama at Birmingham, said in the Sept. 16 release.
“Like other chronic diseases, we need a range of treatment options to address the individual needs of people with obesity, such as their own specific response to treatment," Garvey said.
The data unveiled by Novo this morning come from the same trial that delivered the initial CagriSema data. The multipronged study assessed regimens of either CagriSema, cagrilintide or semaglutide versus placebo in 3,417 adults with one or more obesity-related comorbidities.
Despite cagrilintide as a monotherapy appearing to be less effective as a weight loss treatment than Wegovy, Novo’s plan is to launch a phase 3 trial specifically for cagrilintide in the fourth quarter.
“In our clinical trials, cagrilintide has provided substantial weight loss, in a distinct manner compared to approved obesity medications, and appears well-tolerated,” Novo Chief Scientific Officer Martin Holst Lange, M.D., Ph.D., said in the company release.
“We’re excited that these data, the first phase 3 data of a next-generation amylin therapy, show promise and we look forward to further investigating cagrilintide’s potential in the dedicated phase 3 RENEW programme,” Holst Lange added.
Amylin has emerged as the next hot target in obesity, with AbbVie and Roche buying their way into the race with multibillion-dollar deals. Meanwhile, Eli Lilly posted early-stage data for its own amylin candidate this summer that tied the drug to 11.3% weight loss at 12 weeks.
While analysts praised Lilly’s data at the time, some questioned whether amlyins would be able to deepen weight loss in the same way that GLP-1s have demonstrated. The fact Novo’s cagrilintide struggled to get beyond 12% weight loss over a longer period of 68 weeks suggests these concerns may have some validity.
Still, Novo’s shareholders appeared satisfied, sending the company’s share price up a mild 3% to $57.30 in the wake of the pre-market readout Tuesday morning readout from a Monday closing price of $55. The pharma’s stock has lost a third of its value so far this year against a backdrop of disappointing obesity drug sales, a leadership shake-up and significant layoffs.
Editor's note: This story was updated with more information at 11:20 a.m. ET on Sept. 16.