Eli Lilly's weight-loss drug passes 2nd trial with flying colors, setting up likely approval

Eli Lilly’s trending weight loss candidate tirzepatide has scored its second pivotal trial win—once again with impressive results.

Also known as Mounjaro when marketed as a Type 2 diabetes treatment, tirzepatide helped diabetic patients who are obese or overweight lose up to 15.7% of their body weight in the phase 3 SURMOUNT-2 trial, Lilly said Wednesday.

Tirzepatide performed significantly better than placebo on various weight loss and metabolic measurements. The SURMOUNT-2 study met its two co-primary objectives and all key secondary endpoints, Lilly said.

The SURMOUNT-2 success adds to tirzepatide’s previous positive readout from the SURMOUNT-1 trial in non-diabetic patients. Armed with results from the two phase 3 trials, Lilly said it will wrap an FDA rolling submission for the drug in adults with obesity or who are overweight in the coming weeks. An approval could come as soon as late 2023, the company said.

In SURMOUNT-2, tirzepatide achieved the 15.7% average weight reduction when given at the 15-mg maintenance dose after 72 weeks of treatment. Even at a lower 10-mg dose, tirzepatide takers experienced an average 13.4% of weight loss. Patients who received placebo experienced a 3.3% average reduction in body weight.

The analysis only considered efficacy while patients were on treatment, but a separate analysis looked at those who discontinued treatment. In that analysis, the drug was associated with an average body weight reduction of 14.7% for the 15-mg dose and 12.8% for the 10-mg dose, versus 3.2% for placebo.

Either way, tirzepatide’s weight-loss numbers look better than those achieved by Novo Nordisk’s rival drug Wegovy in its own trial. In the phase 3 STEP 2 study in obese or overweight patients with Type 2 diabetes, Wegovy led to an average weight loss of 9.6%, compared with 3.4% for placebo, after 68 weeks of treatment.

Previously, in their respective nondiabetic obesity trials, tirzepatide at the 15-mg dose led to an average 21% weight reduction, whereas Wegovy managed a 15% change. The magnitude of tirzepatide’s improvement over placebo was also greater.

As for SURMOUNT-2’s other co-primary endpoint, 86.4% of people taking high-dose tirzepatide—and 81.6% on the lower dose—enjoyed at least 5% body weight reduction. Only 30.5% of those taking placebo could say that.

In addition, more tirzepatide takers achieved at least 15% weight reduction compared with those on placebo. The drug also did better at reducing blood sugar and on other cardiometabolic measures, which Lilly said were similar to Mounjaro’s performance in its diabetes trials.

Still, despite tirzepatide’s seemingly better efficacy than Wegovy, cross-trial comparisons pose some intrinsic problems caused by different patient characteristics. Having likely already seen the SURMOUNT-2 results, Lilly last Friday registered a new phase 3 trial dubbed SURMOUNT-5 to test tirzepatide directly against Wegovy.

Based on the SURMOUNT-1 showing, Cowen analysts in November labeled tirzepatide as potentially the “preferred obesity drug." Feedback from expert consultants and physicians suggests that tirzepatide will likely become the most prescribed obesity drug within five years, they said.

Besides the two SURMOUNT trials supporting an FDA submission, Lilly is also pairing tirzepatide with intensive habit modification therapy in the SURMOUNT-3 trial. Further, SURMOUNT-4 is evaluating the benefit of continued tirzepatide treatment over a longer period. Results from both studies are expected this year, Lilly said Wednesday.