The unstoppable march of Eli Lilly’s tirzepatide continues. Having previously shown the dual GIP/GLP-1 agonist reduces the weight of people with diabetes, Lilly has now delivered a hit in its first phase 3 pure play obesity trial, putting Novo Nordisk’s Wegovy on notice that a serious challenger may be on the horizon.
Evidence that tirzepatide poses a threat to Wegovy and Ozempic, respectively the obesity and diabetes versions of Novo’s GLP-1 drug semaglutide, emerged a little more than one year ago with the delivery of data from SURPASS-2. That pivotal trial found tirzepatide beat semaglutide in terms of effect on blood sugar and weight loss, making it a double threat to Novo’s blockbuster molecule.
The latest in Lilly’s long series of data drops comes from SURMOUNT-1, the first pivotal, global phase 3 to evaluate tirzepatide in obese or overweight adults who have at least one comorbidity but don’t have diabetes. Lilly compared the effect of three doses of tirzepatide to placebo over 72 weeks.
Average weight reductions ranged from 16% at the low, 5-mg dose, to 22.5% at the high, 15-mg dose. The average weight reduction in the placebo group was 2.4%, causing the study to meet its primary goal.
“Tirzepatide is the first investigational medicine to deliver more than 20% weight loss on average in a phase 3 study, reinforcing our confidence in its potential to help people living with obesity,” Jeff Emmick, vice president of product development at Lilly Diabetes, said in a statement. “Obesity is a chronic disease that requires effective treatment options.”
To put the results in context, Novo linked semaglutide to a 14.9% average weight reduction in STEP-1, a 68-week clinical trial of nondiabetic patients with obesity or who are overweight and have at least one weight-related comorbidity. In SURMOUNT-1, average weight loss ranged from 16 kg to 24 kg, depending on the dose. The placebo arms of the two trials performed comparably.
Cross-trial comparisons can be unreliable, but the available clinical data suggest tirzepatide has a shot at disrupting the obesity market. Between 89% and 96% of participants on tirzepatide had a 5% or greater body weight reduction, compared to 28% in the placebo group and 86% in the semaglutide study. Lilly also reported that 55% and 63% of people on, respectively, the middle and high doses of tirzepatide had a 20% or greater weight reduction, versus 1.3% of their peers on placebo and 32% in STEP-1.
The top-line safety and tolerability results shared by Lilly are free from red flags. The most commonly reported adverse event at the high dose was nausea—31% at the high dose—followed by diarrhea and vomiting at 23% and 12%, respectively. Lilly is yet to share a detailed look at the data but said events were generally of mild to moderate severity and happened during the dose-escalation period. The rates of discontinuation because of adverse events were 4% to 7% on tirzepatide versus 3% for placebo.
While the study suggests tirzepatide causes unpleasant side effects in some people, the findings are in line with expectations. The Wegovy label lists adverse event rates of 44% for nausea, 30% for diarrhea and 24% for vomiting. Seven percent of patients on Wegovy discontinued because of adverse events.
Lilly filed for FDA approval of tirzepatide in adults with Type 2 diabetes late last year, putting it on track to receive a decision over the summer. The anticipated approval will kick off the first part of an anticipated two-stage rollout, in which Lilly will first target diabetes before later expanding into obesity.
The latest tirzepatide data exceeded the already-high expectations, Mizuho analyst Vamil Divan said in an April 28 note. “The tolerability profile appears generally inline with expectations, and the combination of the two suggests a multi-billion dollar opportunity for the drug in the obesity indication, on top of the multi-billion dollar opportunity it already likely has in patients with diabetes,” Divan said.