ADA: Novo continues effort to rehabilitate CagriSema
Novo Nordisk has reported new data from its phase 3 programme for weight-loss therapy CagriSema, trying to restore confidence in the drug after earlier readouts disappointed investors.
Presenting results from the REDEFINE 1 and REDEFINE 2 studies at the American Diabetes Association (ADA) congress in Chicago, Novo Nordisk pointed to a good tolerability profile for CagriSema and encouraging efficacy as it prepares to file for approval of the drug in the first quarter of 2023.
An earlier reveal of data from the studies of CagriSema – which combines the active ingredient in Novo Nordisk's current obesity therapy Wegovy (GLP-1 agonist semaglutide) with experimental amylin agonist cagrilintide – caused the company's share price to fall sharply, wiping tens of billions of dollars off its valuation. Shortly afterwards, the company parted ways with chief executive Lars Fruergaard Jørgensen.
The sell-off stemmed from fears that CagriSema missed ambitious weight-loss targets of 25% in the two phase 3 trials and, as a result, would struggle to compete with El Lilly's rival obesity therapy Zepbound (tirzepatide), which bested Wegovy in a head-to-head study.
That was in part because the company had failed to explain that the trials allowed patients to stick on a lower dose to help limit side effects, rather than titrating up to a full target dose, which pegged the mean weight loss achieved back to 22.7%.
A new analysis at the ADA suggests that, if all participants adhered to CagriSema treatment, 40.4% achieved a body weight reduction of 25% or more and 23.1% lost at least 30%.
In a surprising finding, the studies showed that patients who chose to stick with a lower dose lost more weight on average, which the investigators said likely reflected individual responsiveness and variability in the clinical response to treatment to the drug.
"These findings may be relevant for clinical practice, since dosing is often adjusted on the basis of individual needs and clinical judgment to achieve the degree of weight loss that promotes health," the REDEFINE 1 triallists wrote in a paper on the study, published in the New England Journal of Medicine, to coincide with the ADA presentation.
Novo Nordisk is emphasising that most patients taking CagriSema had mild-to-moderate side effects that were similar to Wegovy, with a more robust effect on weight loss and very low discontinuation rates of 6% and 8.4%, respectively, in REDEFINE 1 and 2.
In a nutshell, the results could point to a benefit of slower, more gradual weight loss that mitigates side effects, is more likely to encourage patients to stick with treatment, and ameliorates other effects of rapid weight loss on the body.
Novo Nordisk is running another study called REDEFINE 11 that is focusing on a full dose of CagriSema and a longer treatment duration, and is also running a cardiovascular outcome study.
Oral amycretin data
CagriSema is delivered as a once-weekly subcutaneous injection, like Wegovy and Zepbound, and Novo Nordisk also presented data at ADA on its oral weight-loss candidate amycretin, which combines GLP-1 and amylin agonism in a single molecule.
Data from a phase 1 trial showed that oral amycretin achieved weight loss of up to 13.1% over 12 weeks, compared to 1.2% with placebo. Meanwhile, a phase 1/1b study of a once-weekly injectable version of the drug achieved a 24.3% weight reduction after 36 weeks at the highest dose tested. Both formulations are now being advanced into phase 3.
