A blockbuster Eli Lilly drug for type 2 diabetes now has an additional FDA approval in chronic weight management, a regulatory decision that positions the pharmaceutical giant to more directly compete in cardiometabolic conditions against a Novo Nordisk molecule that has become a sales juggernaut in its own right.
Lilly’s new drug is the same as its type 2 medication Mounjaro, but it will be marketed under the brand name Zepbound. The Indianapolis-based drugmaker expects Zepbound will become available in the U.S. by the end of this year.
The FDA approved Zepbound as a way to help patients lose weight and keep it off. The Wednesday regulatory decision covers obese adults with a body mass index of 30 or greater. It may also be prescribed to overweight adults who have a BMI of 27 or greater and at least one weight-related problem, such as hypertension, type 2 diabetes, cardiovascular disease, or obstructive sleep apnea. The drug, administered as a once-weekly injection, is intended for use alongside diet and exercise, similar to Mounjaro’s approved use in type 2 diabetes.
The main active ingredient in both Mounjaro and Zepbound is tirzepatide, a peptide designed to bind to this GLP-1 receptor. Doing so stimulates the secretion of the blood sugar-regulating hormone insulin, an effect that was the basis for tirzepatide’s approval in type 2 diabetes last year. But activating GLP-1 also regulates appetite. The drug’s effect of helping people feel more full and eat less was the basis for its additional approval in weight management.
Novo Nordisk’s diabetes drug Ozempic and weight loss drug Wegovy work the same way, employing a peptide called semaglutide to hit GLP-1. But unlike semaglutide, Lilly’s peptide also simultaneously binds to another receptor called GIP. Nonclinical research suggests activating GIP may further help patients manage how much they eat.
The FDA decision for Zepbound is based on the results of two placebo-controlled studies enrolling 2,519 total patients who were obese or overweight and had at least one weight-related condition. Those participants were randomly assigned to receive one of three doses of the study drug or a placebo. At 72 weeks, participants at all three dose levels showed statistically significant weight loss compared to the placebo arm.
The larger of the two clinical trials enrolled adults without diabetes. At baseline, the average body weight was 105 kg (231 pounds) and the average BMI was 38. The FDA said participants in this study who randomly received the highest dose of Zepbound lost an average 18% of their body weight compared to those given a placebo.
“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death such as heart disease, stroke and diabetes,” John Sharretts, director of the Division of Diabetes, Lipid Disorders, and Obesity at the FDA said in a prepared statement. “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”
Side effects reported in the clinical studies include nausea, diarrhea, vomiting, constipation, and stomach discomfort and pain. The drug’s label carries a black box warning that notes the drug caused thyroid C-cell tumors in rat studies, adding that this risk in humans is unknown. The same warning is flagged on Mounjaro’s label. One key difference between the two labels is Zepbound’s cautions that the drug may lead to suicidal thoughts and behavior. That warning is also found on Wegovy’s label.
Just like Mounjaro, Lilly will supply Zepbound in six doses that can be administered by an autoinjector pen. The new drug’s $1,059.87 list price is in line with Mounjaro’s price and about 20% below the cost of Novo Nordisk’s Wegovy for weight loss.
In a note sent to investors, Leerink Partners analyst David Risinger wrote that Lilly explained its pricing of Zepbound at a discount to Wegovy as a strategy to increase access to the drug. Employers primarily focus on list price as they do not have much visibility on net price, which is the list price minus any rebates or discounts. Lilly wants to drive access to Zepbound in the obesity market, and the company’s management told Leerink that “obesity is very different from a market like diabetes in which employer opt-ins are not a dynamic.”
Mounjaro, approved last year, is already Lilly’s second-largest seller behind only the diabetes drug Trulicity. In its report of third quarter 2023 financial results last week, Lilly reported Mounjaro accounted for $1.4 billion in sales. For the year to date, the drug generated more than $2.9 billion in revenue. Adding Zepbound can help Lilly catch up to Novo Nordisk.
In its quarterly financial update last week, Novo Nordisk reported Ozempic accounted for 65.6 billion Danish kroner (about $9.4 billion) in sales. Wegovy generated 21.7 billion Danish krone (about $3 billion) in revenue.
Photo by Eli Lilly