Novo charts course ahead for CagriSema after lacklustre data
Martin Holst Lange, Novo Nordisk's head of development.
Novo Nordisk has acknowledged that the first phase 3 readout for new obesity hopeful CagriSema was hard to interpret and disappointed investors, but it has a plan to revitalise the programme.
In its fourth-quarter results update, the Danish drugmaker's chief executive, Lars Fruergaard Jørgensen, said: "We remain confident in its potent biology and look forward to further exploring its potential and to making it available to patients."
The key to unlocking the drug's potential will be a new trial due to start in the first half of this year that will include a new personalised approach to dosing with CagriSema and a longer period of follow-up, according to Martin Holst Lange, Novo Nordisk's head of development.
CagriSema combines the GLP-1 agonist semaglutide in Novo Nordisk's blockbuster weight-loss drug Wegovy with dual amylin and calcitonin receptor agonist cagrilintide.
The company is hoping that the combination can improve on the efficacy of Wegovy and help defend its obesity franchise against Eli Lilly – whose dual GIP/GLP-1 agonist Zepbound (tirzepatide) proved more effective at reducing weight in a head-to-head trial – as well as future rivals.
CagriSema slightly underperformed expectations in the REDEFINE 1 study reported in December, achieving a headline reduction in weight of 22.7% at 68 weeks, which fell short of the 25% that Novo Nordisk was hoping for and was roughly on par with the results seen with Zepbound.
Lange explained on a conference call that one reason for the miss was a flexible treatment protocol that allowed patients to scale down their dosing if, for example, they experienced side effects like gastrointestinal upset, and it has emerged that only around 57% of patients reached the maximum target dose.
That said, there were fewer dropouts due to side effects with CagriSema than in previous trials of Wegovy, at approximately 3.6% and 4.5%, respectively, so there does not seem to be a serious problem with toxicity.
Among this high-dose group, weight loss had not started to plateau at the 68-week timepoint, which "suggests that additional weight loss could be achieved with a trial of longer duration," he said.
Meanwhile, rather than just reducing dose, the plan in the new trial is to allow for CagriSema to be increased again if side effects resolve, which Novo Nordisk believes could "potentially enhance efficacy of CagriSema while maintaining a favourable safety profile."
The new trial will be called REDEFINE 11 and is due to start in the first half of this year. In the meantime, attention is on the results of the REDEFINE 2 trial before the end of the first quarter – as Novo Nordisk prepares for a possible CagriSema filing in early 2026 – along with progress with high-dose versions of Wegovy and oral semaglutide product Rybelsus, as well as oral amycretin, which is in phase 1/2 testing.
