Novo Nordisk fights back at Lilly with Wegovy combo trial against Zepbound in obesity

In response to an onslaught from Eli Lilly, Novo Nordisk is escalating the obesity market battle with a new head-to-head trial against its archrival.

Novo has unveiled a new phase 3 trial pitting CagriSema, a fixed-dose combination of Wegovy and the investigational drug cagrilintide, against Lilly’s Zepbound in people with obesity, according to a clinicaltrials.gov entry.

The study, coded REDEFINE 4, plans to enroll 800 patients, and those with diabetes are excluded. Its primary goal is to evaluate how well the two companies’ therapies could help people lose weight relative to each other after 72 weeks of treatment.

In addition, the trial will measure the number of patients in each arm who’ve achieved at least 25% or 30% weight reduction at the end of treatment. Other secondary endpoints include changes in cholesterol levels, triglycerides, waist circumference, systolic blood pressure and serious side effects.

The trial is only part of the clinical program for CagriSem in obesity, but not a pivotal trial needed for regulatory submission, a Novo spokesperson told Fierce Pharma.

The Novo trial comes about seven months after Lilly launched a head-to-head phase 3 study testing Zepbound—also known as Mounjaro in diabetes treatment—against Wegovy in obese patients or those who are overweight with certain health conditions.

Zepbound, a.k.a. tirzepatide, gained an FDA nod last week for chronic weight management in people with obesity or who are overweight. The GIP/GLP-1 duo agonist has shown better weight reduction results than Wegovy did in separate trials.

Novo believes that the addition of cagrilintide could turn the tide for Wegovy in this weight loss rivalry. CagriSema coadministers 2.4mg cagrilintide with 2.4mg Wegovy as a fixed-dose, once-weekly injection. The new obesity trial pits CagriSema against the highest, 15mg dose of Zepbound.

Cagrilintide is a long-acting amylin analog. Phase 2 data published in June showed that once-weekly CagriSema led to an average 15.6% bodyweight reduction at week 32 among Type 2 diabetes patients who were overweight or obese. By comparison, people on cagrilintide alone achieved an average 8.1% loss, while Wegovy hit a 5.1% decrease. The study was small with only 92 participants.

Before the new CagriSema-Zepbound obesity trial, Novo had already kicked off a series of phase 3 program for CagriSema in Type 2 diabetes in 2022. One of the planned trials, REIMAGINE 4, is expected to be a head-to-head between CagriSema and Lilly’s Mounjaro.

One important difference between the current Novo trial and Lilly’s is that the CagriSema study only allows obese people with a body mass index (BMI) of at least 30kg/m2, while the SURMOUNT-5 trial between Zepbound and Wegovy includes overweight people with BMI of 27kg/m2 and weight-related comorbidities.

Novo didn’t immediately respond to a Fierce Pharma request for comment on the trial design and the Danish company’s regulatory plan for CagriSema in obesity.

Lilly also has a long-acting amylin agonist in phase 1 testing, according to the company’s website. It’s not clear if Lilly will or can combine the candidate with tirzepatide.

The weight loss market is getting increasingly competitive with Lilly’s launch of Zepbound. Also last week, AstraZeneca unveiled a deal to purchase an oral GLP-1 drug from China’s Eccogene. At least the market looks big enough for multiple players. Both Novo and Lilly are struggling to meet demand, and major manufacturing expansions are underway at both firms.

Editor's Note: The story has been updated with a comment from a Novo Nordisk spokesperson.