Eli Lilly announces ATTAIN-MAINTAIN trial met primary, secondary endpoints

Eli Lilly (LLY) announced topline results from the ATTAIN-MAINTAIN trial. The Phase 3 study evaluated orforglipron, an investigational, once-daily oral small molecule glucagon-like peptide-1 receptor agonist, for weight maintenance over 52 weeks after initial treatment for 72 weeks with the highest tolerated doses of Wegovy or Zepbound, in participants from SURMOUNT-5 who were offered the opportunity to be re-randomized to receive orforglipron or placebo. At one year, orforglipron met the primary and all key secondary endpoints compared to placebo, delivering superior weight maintenance as an adjunct to a healthy diet and physical activity, using the efficacy estimand and modified treatment-regimen estimand.In the study, orforglipron met the primary endpoint of superior percent maintenance of body weight reduction compared to placebo, among SURMOUNT-5 participants who previously reached a body weight plateau. In pre-specified analyses at 52 weeks, participants who switched to orforglipron from Wegovy maintained their previously achieved weight loss with an average difference of 0.9 kg, while those who switched to orforglipron from Zepbound maintained their previously achieved weight loss with an average difference of 5 kg, using the efficacy estimand. In post-hoc analyses at 24 weeks, the last time point before placebo participants were eligible for orforglipron as rescue therapy, the change in body weight from ATTAIN-MAINTAIN baseline for patients switching to orforglipron from Wegovy was -0.1 kg vs. 9.4 kg for placebo. Likewise, for patients switching to orforglipron from Zepbound, the change from baseline was 2.6 kg vs. 9.1 kg for placebo. The overall safety and tolerability profile of orforglipron in ATTAIN-MAINTAIN was consistent with previous orforglipron Phase 3 studies. The most common adverse events were gastrointestinal-related and generally mild-to-moderate in severity. Discontinuation rates due to adverse events for patients randomized to placebo or orforglipron were 4.8%, 7.6%, 7.2% and 6.3%. No hepatic safety signal was observed. Detailed results from the ATTAIN-MAINTAIN trial will be presented at a future medical meeting and published in a peer-reviewed journal next year. Lilly has submitted a new drug application to the FDA for orforglipron for the treatment of adults with obesity or overweight. Orforglipron was granted a Commissioner’s National Priority Voucher from the FDA.