F.D.A. Approves New Obesity Drug Tirzepatide That Will Compete With Wegovy
The Food and Drug Administration on Wednesday approved an obesity drug from the company Eli Lilly that will be a direct competitor to the wildly popular Wegovy.
The drug is called tirzepatide and will be sold under the name Zepbound. It joins a class of new medications that are transforming obesity, a condition that affects 100 million American adults and is linked to a spectrum of diseases including diabetes, heart disease, sleep apnea, liver disease, kidney disease and joint pain.
Patients who used tirzepatide lost an average of 18 percent of their body weight, according to the F.D.A., when it was taken at its highest dose in a drug trial. That’s compared with Wegovy, manufactured by Novo Nordisk, which produced an average 15 percent weight loss.
Tirzepatide is already approved for diabetes under the brand name Mounjaro where it competes with Novo Nordisk’s diabetes drug semaglutide, known better as Ozempic. But until now, Wegovy — also semaglutide but with a higher maximum dose than Ozempic — was the only approved drug that could safely elicit substantial weight loss in people with obesity alone.
Side effects with Zepbound, similar to those with Wegovy, Ozempic and Mounjaro, are mostly gastrointestinal, like nausea and diarrhea. Most patients tolerated or overcame them.
In a news release, Dr. John Sharretts, director of the Division of Diabetes, Lipid Disorders and Obesity in the F.D.A.’s Center for Drug Evaluation and Research, said, “In light of increasing rates of both 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 be difficult to imagine two medications like semaglutide and tirzepatide that lead to weight loss that previously was only seen when people had bariatric surgery,” referring to a surgical treatment that is a proven effective treatment for obesity.
The approval comes at a time when Novo Nordisk is unable to produce enough Wegovy to satisfy the huge demand for the drug. Tirzepatide, which patients take by a self-administered injection once a week, as they do with Wegovy, could ease those shortages.
Competition could also result in lower net prices for both drugs, or how much payers actually spend on them. The prices are high for Wegovy — with a list price up to $1,349 every four weeks in one recent analysis, and a net price around $700. Zepbound is starting with a list price of around $1,060, according to Eli Lilly.
“You’d want the price competition to come sooner rather than later,” said Craig Garthwaite, a health care economist at Northwestern University. Once people start taking one of these drugs, he said, “they get locked in.” They resist switching even if a competing drug costs less.
Development of Zepbound began in 2017 with a small study involving 300 people with type 2 diabetes. After 3 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 sponsored by Eli Lilly of tirzepatide in 2,539 people with obesity.
In a packed room at a meeting of the American Diabetes Association last year, the study’s principal investigator, Dr. Ania Jastreboff of Yale, revealed the results. More than half the patients receiving the highest dose lost at least 20 percent of their body weight.No drug has ever before shown such a profound weight loss.
For Eli Lilly, the results were a culmination of research that began a decade ago. But like Novo Nordisk, the company was trying to produce a new diabetes drug.
“Obesity wasn’t a main focus for us,” Dr. Daniel Skovronsky, the chief scientific and medical officer at Eli Lilly, said, adding that “it was not seen as a commercial opportunity.”
The sad history of weight loss drugs was a lesson, he thought. “There had never been a successful obesity drug,” he said, “and previous drugs didn’t cause enough weight loss to have an impact on peoples’ health.”
But researchers at Eli Lilly had started investigating a diabetes drug that combined two molecules. One molecule acts like a hormone, GLP-1, that prompts the body to secrete insulin when blood sugar rises. That was similar to the effects of Novo Nordisk’s Ozempic and Wegovy. And like those drugs, it also suppresses appetite.
But more than one hormone is involved when the body regulates blood sugar, so the company’s scientists decided to try combining the molecule that mimics GLP-1 with a second molecule that acts like the gut hormone GIP. Although GIP has a more modest effect when given alone, it amplified GLP-1’s effect when the two hormone mimics were combined.
In mice, the two-drug combination not only lowered blood sugar but also had a profound effect on weight. It was “the most weight loss we’d ever seen,” Dr. Skovronsky said.
The company’s scientists tested the drug in healthy volunteers. Even though they did not have obesity, the people lost weight.
Suddenly, Eli Lilly’s opinion of studying weight loss changed.
“We thought, ‘This medicine can change the world,’” Dr. Skovronsky said. “We said: ‘This is the one. This is our priority.’”
They decided to speed development with an approach known as “investing at risk” in which they do not wait for each stage of testing to be completed before starting the next, and in which they start building manufacturing capability before studies are completed. The result was a pace that was a record for the company — six years from the first dose in human volunteers to F.D.A. approval. A similar strategy was also used to speed up Covid vaccine development.
The hope is that Zepbound can reduce the chances that people with obesity will develop the potentially deadly complications that accompany the condition.
But Zepbound is only the beginning for Eli Lilly. The company and other pharmaceutical manufacturers are working on drugs that could be even more powerful.
The next Lilly drug adds glucagon, another gut hormone, to the two in Zepbound. It apparently stimulates metabolism and draws fat out of the liver.
And, like Novo Nordisk and other companies, Eli Lilly is working on a pill form of tirzepatide. It is undergoing clinical testing.
Making injectable drugs is complicated and challenging. Pills are simpler and cheaper, which could improve the supply problem that has affected patients who use Ozempic and Wegovy.
It is estimated that by 2030, a billion people in the world will have obesity.
“All the companies in the world cannot make that many injections,” Dr. Skovronsky said. “Clearly if we are going to meet the needs of the global epidemic, we need oral drugs.”