Lilly’s Orforglipron Helps Sustain Weight Loss After Switching from Injectable to Oral GLP-1 Therapy in Pivotal Phase 3 Trial
Eli Lilly and Company today announced positive topline results from the ATTAIN-MAINTAIN trial. The Phase 3 study evaluated orforglipron, an investigational, once-daily oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist, for weight maintenance over 52 weeks after initial treatment for 72 weeks with the highest tolerated doses of Wegovy (semaglutide) or Zepbound (tirzepatide), 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.1,2
“Obesity is a chronic, progressive disease, and sustaining weight loss remains a significant challenge for many,” said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. “ATTAIN‑MAINTAIN showed that orforglipron, a once-daily oral GLP-1, helped people maintain the weight they worked hard to lose. Participants in this study were able to switch directly from the highest tolerated doses of available injectable therapies onto oral doses of orforglipron. If approved for the treatment of obesity, orforglipron could provide a convenient alternative for the millions of individuals living with obesity around the globe to continue their long-term health journey.”
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 5.0 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 Lilly 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.
| Average Weight at Baseline and ATTAIN-MAINTAIN Results | ||||
| Wegovyiii to Orforglipron | Zepboundiii to Orforglipron | |||
| Starting weighti(at start of SURMOUNT-5) | 113.5 kg (250.2 lbs) | 115.8 kg (255.3 lbs) | ||
| Weight at switch to orali(at start of ATTAIN-MAINTAIN) | 95.0 kg (209.4 lbs) | 90.9 kg (200.4 lbs) | ||
| Weight after 52 weeks of oral maintenanceii(at end of ATTAIN-MAINTAIN) | 95.9 kg (211.4 lbs) | 95.9 kg (211.4 lbs) | ||
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% (orforglipron from Wegovy), 7.6% (placebo from Wegovy), 7.2% (orforglipron from Zepbound) and 6.3% (placebo from Zepbound). 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 U.S. Food and Drug Administration (FDA) for orforglipron for the treatment of adults with obesity or overweight. Orforglipron was granted a Commissioner’s National Priority Voucher from the U.S. FDA.
Source Link: https://investor.lilly.com/
