Eli Lilly’s weight-loss drug retatrotide passes first late-stage study

Eli Lilly The next-generation obesity drug achieved what appears to be the highest weight loss yet in a late-stage trial while reducing osteoarthritis pain in the knee, clearing the first of several upcoming studies on the weekly injection, she said Thursday.

The highest dose of the drug helped patients with obesity and a type of knee osteoarthritis lose an average of 23.7% of their body weight at week 68, when all participants were analyzed, including those who stopped treatment. The company said Some patients lost so much weight that they decided to withdraw from the trial.

When evaluating only patients who continued to take the drug — essentially the best-case scenario — the higher dose resulted in an average of 28.7% weight loss.

“It’s incredible,” said Dr. Carolyn Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital. “Now, we have a drug that rivals the benefits of weight loss through surgery.”

Apovian said Eli Lilly appears to be positioning the drug strategically for people who are obese, or have a BMI higher than 35 or 40. She noted that the company said 84% of patients in the trial had a BMI higher than that number in the trial.

Shares of Eli Lilly rose more than 3% on Thursday.

This is the first late-stage data on retatrotide, which works differently than existing injections and appears to be more effective. Eli Lilly is betting big on retatrutide as the next pillar of its obesity portfolio following its weight-loss injection Zepbound and its upcoming pill. But it is still unclear when the drug could enter the market.

It’s an important part of the drugmaker’s plan to maintain a majority of its market share Novo Nordisk In the booming market for weight loss and diabetes medications. Some analysts estimate that this sector could be worth about $100 billion by the 2030s.

Retatrutide also met the trial’s other main goal of reducing pain from knee osteoarthritis — a common condition that wears down joint cartilage and leads to pain and stiffness — by up to 62.6% on average when all patients were analyzed, based on a widely used survey. Eli Lilly said that more than 1 in 8 patients who took the drug were completely free of knee pain by the end of the trial.

One concern with current weight loss medications is that they can lead to a loss of lean muscle mass. But the results show that in obese adults, you can improve physical function with retaretide, Apovian said.

The results appear to have exceeded Wall Street expectations. In a note before the results, BMO Capital Markets analyst Evan Segerman said his baseline assumption was for the drug to show weight loss of 20% to 23%, with at least a 50% reduction in knee pain.

Kenneth Custer, president of Lilly Cardiometabolic Health, said in a statement that the company believes retaretide “could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis.”

In a note Thursday, JPMorgan analyst Chris Schott said the tolerability data for retaretide, or how well patients cope with the treatment, is “somewhat worse compared to Zepbound, although not surprising, in our view.”

Nearly 18% of patients taking the highest dose of the drug discontinued treatment due to side effects, compared with 4% of those in the placebo group. Eli Lilly said these dropout rates were “highly related” to patients’ initial BMI, and included study discontinuations due to “perceived excessive weight loss.”

Among those with a BMI of 35 or higher who took the highest dose, 12% discontinued treatment. That number is closer to the dropout rates seen in trials of Eli Lilly’s weight-loss drug Zipbond, Schott said. Novo NordiskObesity injections Wegovy.

In a separate note Thursday, BMO’s Segerman said the discontinuation rates “appear to highlight that the speed and strength of weight loss was excessive for some patients with low BMI.” But he said: “All the results are impressive.”

About 43% of patients taking the highest dose experienced nausea, while about 33% and 20.9% developed diarrhea and vomiting, respectively. More than 1 in 5 patients taking the highest dose also experience dysesthesia, an unpleasant nervous sensation. The company said that symptoms were generally mild for patients and rarely led to them stopping treatment.

The study, called TRIUMPH-4, did not focus on weight loss alone, which means other trials designed specifically for this outcome could produce different or higher results. Eli Lilly expects to report results from seven additional Phase 3 trials of the drug by the end of 2026.

Retatrotide, called the “Triple G” drug, works by mimicking three hormones that regulate hunger — GLP-1, GIP, and glucagon — instead of just one or two like existing treatments. This appears to have stronger effects on a person’s appetite and food satisfaction than other treatments.

Tirzepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk semaglutide, the active ingredient in Wegovy, mimics only GLP-1.

High doses of terzepatide helped obese patients lose approximately 20.9% of their body weight on average in late-stage studies, when all patients were analyzed regardless of discontinuations.

While Eli Lilly is gaining ground in this space, its main competitor, Novo Nordisk, is racing to catch up. In March, Novo Nordisk said it had agreed to pay up to $2 billion for the rights to an early experimental drug from Chinese pharmaceutical company United Laboratories International.

The newly acquired Novo Nordisk drug is an obvious potential competitor to retaretide because it similarly uses a three-pronged approach to promote weight loss and regulate blood sugar. But Novo Nordisk’s treatment is still in the early stage of development, meaning it will take several years before it reaches patients.