The data suggest the high dose nearly closes the efficacy gap with Zepbound.
A high dose of Novo Nordisk’s obesity drug Wegovy caused more weight loss than the approved regimen in a Phase III trial, the company said Friday. However, the data suggest Eli Lilly’s rival GLP-1 drug Zepbound may still have an edge over Wegovy.
Wegovy, the weight-loss brand of semaglutide, has a recommended maintenance dose of 2.4 mg. Novo ran the Phase III STEP UP trial to evaluate the effect of increasing the maximum dose to 7.2 mg. The trial randomized 1,407 adults with obesity, but not diabetes, to receive either 7.2 mg or 2.4 mg of semaglutide or placebo.
After 72 weeks of weekly injections, patients on the 7.2 mg dose had lost 18.7% of their body weight. Novo saw weight loss of 15.6% at the 2.4 mg dose and 3.9% on placebo. One-third of patients on the high dose lost at least 25% of their weight, compared to 16.7% of people taking the lower dose. The results suggest launching the higher dose could increase the weight loss people experience on Wegovy, Novo said.
Boosting efficacy could help Novo in its fight for market share. Zepbound beat Wegovy in a head-to-head Phase IIIb trial in December. Data from that trial, SURMOUNT-5, showed that patients on Zepbound lost 20.2% of their weight over 72 weeks in a Phase III trial—a bit higher than the new Wegovy results. Cross-trial comparisons can be misleading, however.
Martin Holst Lange, executive vice president of development at Novo, set out his expectations for the 7.2 mg dose at the company’s capital markets day last March. Lange said Novo’s models showed the higher dose could achieve weight loss of 20% to 21% without compromising on safety and tolerability.
Novo reported weight loss of 20.7% in STEP UP when evaluating the effects of semaglutide if all participants adhered to treatment. In that analysis, the 2.4 mg dose achieved weight loss of 17.5%. The placebo result was 2.4%.
“The weight loss exhibited with 7.2 mg semaglutide compares cross-trial to LLY’s Ph3 SURMOUNT-1 tirzepatide up to 22.5% (20.1% pbo-adj.) at the same time point using a similar measure (Jastreboff et. al NEJM 2022). The results give us greater confidence in long-term tirzepatide market share,” Leerink Partners analysts wrote in a Friday note to investors, adding, “We await detailed results from the Ph3b STEP UP trial at a medical conference this year, but we note that historical data showed better cross-trial tolerability for tirzepatide compared to sema’s 2.4 mg dose.”
In its latest announcement, the Danish drugmaker said the 7.2 mg dose appeared to have a safe and well-tolerated profile. The most common adverse events were gastrointestinal, as is typical for GLP-1 drugs, and the vast majority of side effects were mild to moderate and diminished over time. Novo said it will share detailed results, which could provide a clearer look at the tolerability implications of increasing the dose, later this year.
Novo made no mention of CagriSema, its semaglutide combination therapy, in the topline data release, but the results may have implications for this investigational program. Lange said in March that the 7.2 mg data could enable Novo “to go into even higher doses with CagriSema in the life cycle management space.” However, Phase III CagriSema data disappointed investors late last year, sending Novo’s stock down 20%.
The reveal of the 7.2 mg data coincided with the news that the Centers for Medicare and Medicaid Services has chosen semaglutide for its second cycle of price negotiations. The negotiations could lower the price the government pays for Wegovy and Ozempic, the diabetes brand of semaglutide, in 2027.
