- An experimental, triple-acting obesity drug from Eli Lilly helped some patients in a Phase 2 trial lose nearly a quarter of their body after 48 weeks, according to study results presented at a medical meeting Monday and published in the New England Journal of Medicine.
- Patients treated with the highest dose of the drug, an injectable medicine called retatrutide, lost an average of 17.5% of their weight after 24 weeks, versus a 1.6% loss for placebo recipients. The effect size grew as time went on, with Lilly reporting a mean of 24.2% for those patients after 48 weeks.
- As with other drugs like it, retatrutide was associated with gastrointestinal side effects such as nausea and vomiting. Wall Street analysts also flagged the potential for cardiovascular risk, as well as a type of skin sensitivity that occurred in 7% of treated patients compared to 1% of those who got a placebo.
Obesity drug development has quickly become one of the most competitive areas of biopharmaceutical research, with Lilly, Novo Nordisk and a group of would-be rivals racing for dominance of a market some analysts estimate to be worth more than $100 billion globally.
The annual meeting of the American Diabetes Association is the latest forum for the fast-moving competition, and one in which Lilly showcased its investments.
Already, Lilly has brought to market Mounjaro, an injectable medicine that’s approved for diabetes and could be cleared for use as an obesity treatment by the end of the year. Behind Mounjaro is an oral drug, orforglipron, that’s shown weight-loss effects in mid-stage testing that are comparable to injectable treatments.
Retatrutide is next in line and, unlike many obesity drugs in development, targets three hormones. Novo’s Wegovy acts on one, for instance, while Mounjaro homes in on two.
In the study presented at ADA, 338 patients received one of four different doses of retatrutide, or a placebo. At the start of the study, patients had a body-mass index of 30 or higher, or a BMI of 27 to less than 30 as well as a weight-related condition. The trial’s main goal was a change in body weight after 24 weeks. Secondary endpoints included a measure of weight after 48 weeks, as well as weight reductions of 5%, 10%, and 15% or more.
The drug’s effects on weight loss “triggered rare applause” from the crowd at the meeting and “may set a high bar for the next treatment wave” in obesity, wrote Jefferies analyst Peter Welford.
Welford also noted that all patients who received one of the top two doses lost at least 5% of their weight and nearly half of those on the highest dose lost more than 25%. “Remarkably the weight loss slopes continue to decline, suggesting greater effect in Phase 3 is possible,” he wrote.
The findings compare favorably to Mounjaro, which, in one of its Phase 3 trials, led to about a 20% weight loss after 48 weeks, wrote SVB Securities analyst David Risinger. But safety will be closely watched going forward. The study discontinuation rate was 16% for those on the highest dose. The appearance of a skin sensitivity side effect, cutaneous hyperesthesia, “drew attention,” Risinger noted. And “cardiovascular risk could be something to watch for,” he wrote, noting the instance in a single patient of a type of heart rhythm disruption called QT syndrome.
Lilly is investigating retatrutide in a large late-stage program involving at least four trials, among them studies in obesity and chronic weight management. Novo, meanwhile, has a newer medicine known as CariSegma that’s also in Phase 3 testing, and a pill that could be submitted to regulators this year.