Novo Nordisk reported a loss in a head-to-head trial of CagriSema against Lilly’s Zepbound earlier this week. This time around, Lilly’s orforglipron bested Novo’s oral semaglutide in blood sugar control and weight reduction—albeit with a few extra discontinuations as compared to its rival.
Another day, another head-to-head clinical loss for Novo Nordisk, as Eli Lilly’s oral candidate orforglipron bested oral semaglutide at blood sugar control and weight loss in a Phase 3 clinical trial. But Lilly’s offering seemed to spur more discontinuations as compared to Novo’s product, leaving the Danish pharma with a slight edge to hang onto.
In the ACHIEVE-3 trial, Lilly tested orforglipron against Novo’s oral semaglutide pill in patients with type 2 diabetes whose disease is inadequately controlled on metformin. Novo markets the pill as Rybelsus for diabetes and Wegovy for weight loss. In the trial, Lilly’s drug beat Rybelsus on the main and secondary endpoints, showing greater improvements in A1C control and weight loss, according to a Thursday morning press release.
Orforglipron also beat the approved therapy on measures of cardiovascular risk reduction including lowering of different types of cholesterol, blood pressure and triglycerides.
But while orforglipron’s safety data were as expected, according to Lilly, more patients in this cohort discontinued treatment than those taking Rybelsus during the trial. Discontinuations due to adverse events with orforglipron occurred in 8.7% of patients in the 12-mg arm and 9.7% in the 36-mg group, as compared to 4.5% of patients on the 7-mg dose of Rybelsus and 4.9% of those on the 14-mg dose. The most common side effects were nausea, diarrhea, vomiting, indigestion and decreased appetite.
Part of Lilly’s pitch for orforglipron is that it can be taken without any food or water restrictions. The Wegovy pill, meanwhile, must be taken in the morning on an empty stomach and 30 minutes before eating.
This is the second head-to-head trial between the two obesity juggernauts to read out this week. On Monday, Novo reported an own goal when its investigational combo treatment CagriSema fell to Lilly’s Zepbound in a Phase 3 obesity trial. CagriSema achieved 23% weight loss while Lilly’s offering reached 25.5%. The results sent Novo’s shares plummeting.
Head-to-head trials are typically reserved for marketed products as pharmas seek to gain an edge over rivals. Lilly and Novo, locked in one of the fiercest market battles the industry has ever seen, have been performing these studies with their GLP-1 assets early in an effort to secure the crown as the biggest and best weight loss company.
Lilly has come out on top in most of these bets. Novo, on the other hand, had to report the failure of a study it sponsored with the CagriSema-Zepbound match up.
Novo’s oral Wegovy has been on the market since the beginning of the year, already racking up 100,000 prescriptions in what CEO Maziar Mike Doustdar has dubbed one of the most successful pharma launches ever. Rybelsus, on the other hand, was first approved for type 2 diabetes in 2017.
But Lilly is close behind with orforglipron, which was submitted to the FDA late last year. A decision is expected by the end of the second quarter. Today’s data were not included in the submission package.
Editor’s Note: An earlier version of this story incorrectly stated that the study featured Novo’s oral Wegovy. The trial in fact tested Rybelsus, which is the FDA approved version of semaglutide for diabetes. BioSpace apologizes for the error.
