The Food and Drug Administration on Wednesday approved an obesity drug from Eli Lilly that will be a direct competitor to the wildly popular Wegovy.
The drug is called tirzepatide and is sold under the name Zepbound. It joins a class of new drugs that fight obesity, a condition that affects 100 million American adults and is linked to a range of diseases including diabetes, heart disease, sleep apnea, liver disease, kidney disease and joint pain.
Patients taking tirzepatide lost an average of 18 percent of their body weight when taken at the highest dose in a drug study, according to the FDA. In comparison, Wegovy, made by Novo Nordisk, resulted in an average weight loss of 15 percent.
The FDA has approved Zepbound for people with obesity and for people who are overweight and have at least one obesity-related condition.
Tirzepatide is already approved for diabetes under the brand name Mounjaro and competes with Novo Nordisk’s diabetes drug semaglutide, better known as Ozempic. But until now, Wegovy — also semaglutide, but with a higher maximum dose than Ozempic — was the only approved drug that alone could safely produce significant weight loss in people with obesity.
Side effects of Zepbound, similar to those of Wegovy, Ozempic, and Mounjaro, are mostly gastrointestinal in nature, such as nausea and diarrhea. Most patients tolerated or overcame them.
In a press release, Dr. John Sharretts, director of the Division of Diabetes, Lipid Disorders and Obesity in the FDA’s Center for Drug Evaluation and Research: “Given the rising rates of obesity and overweight in the United States, today’s approval addresses an unmet medical need.”
Susan Yanovski, co-director of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases, said: “Just a few years ago, it would have been difficult to imagine two drugs like semaglutide and tirzepatide causing weight loss.” “has previously only been observed when people underwent bariatric surgery” and refers to a surgical treatment that has been shown to be an effective treatment for obesity.
The approval comes at a time when Novo Nordisk is unable to produce enough Wegovy to meet high demand for the drug. Tirzepatide, which patients like Wegovy take once a week as a self-administered injection, could ease these shortages.
Competition could also lead to a decrease in net prices for both drugs or how much payers actually spend on them. The list and net prices are high for Wegovy.
“You want price competition to come sooner rather than later,” said Craig Garthwaite, a health economist at Northwestern University. Once people start taking one of these drugs, “they get locked up,” he said. They are reluctant to switch, even if a competing drug costs less.
Development of Zepbound began in 2017 with a small study of 300 people with type 2 diabetes. After three months, many lost at least 13 percent of their body weight. Eli Lilly presented the data at a diabetes meeting in Germany. Some in the audience gasped.
Then came a large 72-week study of tirzepatide in 2,539 people with obesity, sponsored by Eli Lilly.
In a crowded room at a meeting of the American Diabetes Association last year, the study’s lead researcher, Dr. Ania Jastreboff from Yale, the results. More than half of the patients who received the highest dose lost at least 20 percent of their body weight. Never before has such a significant weight loss been achieved with a medication.
For Eli Lilly, the results were a culmination of research that began a decade ago. But like Novo Nordisk, the company was trying to make a new diabetes drug.
“Obesity was not a major focus for us,” said Dr. Daniel Skovronsky, the chief scientific and medical officer at Eli Lilly, added that “it was not seen as a commercial opportunity.”
The sad story of weight loss drugs was a lesson, he thought. “There has never been a successful anti-obesity drug,” he said, “and previous drugs did not produce enough weight loss to have an impact on people’s health.”
But researchers at Eli Lilly had begun studying a diabetes drug that combined two molecules. One molecule acts like a hormone, GLP-1, which causes the body to release insulin when blood sugar levels rise. This was comparable to the effects of Ozempic and Wegovy from Novo Nordisk. And like these medications, it also suppresses appetite.
However, because the body involves more than one hormone in blood sugar regulation, the company’s scientists decided to combine the molecule that mimics GLP-1 with a second molecule that acts like the gut hormone GIP. Although GIP alone has less effect, it enhances the effect of GLP-1 when the two hormone mimics are combined.
In mice, the combination of two drugs not only lowered blood sugar but also had a profound effect on weight. It was “the greatest weight loss we had ever seen,” said Dr. Skovronsky.
The company’s scientists tested the drug on healthy volunteers. Even though they weren’t obese, people lost weight.
Suddenly, Eli Lilly’s opinion about studying weight loss changed.
“We thought, ‘This drug can change the world,'” said Dr. Skovronsky. “We said, ‘This is it. That’s our priority.’”
They decided to accelerate development using an approach known as “risk investing.” They do this by not waiting for each testing phase to complete before moving on to the next, and by starting to build manufacturing capacity before studies are complete. The result was a record pace for the company – six years from the first dose in human volunteers to FDA approval. A similar strategy has also been used to accelerate the development of Covid vaccines.
The hope is that Zepbound may reduce the risk of people with obesity developing the potentially fatal complications that come with the condition.
But Zepbound is just the beginning for Eli Lilly. The company and other drugmakers are working on drugs that could be even more effective.
The next Lilly drug adds glucagon, another gut hormone, to the two in Zepbound. It apparently stimulates metabolism and removes fat from the liver.
And like Novo Nordisk and other companies, Eli Lilly is working on a pill form of tirzepatide. It is currently undergoing clinical testing.
Manufacturing injectable drugs is complicated and challenging. Pills are simpler and cheaper, which could improve the supply problem affecting patients taking Ozempic and Wegovy.
It is estimated that one billion people in the world will suffer from obesity by 2030.
“All the companies in the world can’t do that many injections,” said Dr. Skovronsky. “If we want to meet the needs of the global epidemic, we clearly need oral medications.”