Eli Lilly and Company has announced positive topline Phase 3 results from Achieve-1, evaluating the safety and efficacy of orforglipron compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. 

 

Orforglipron is the first oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist, taken without food and water restrictions, to successfully complete a Phase 3 trial. If approved, the company is confident in its ability to launch orforglipron worldwide without supply constraints. This would further Lilly's mission to reduce chronic diseases like type 2 diabetes, which is expected to impact an estimated 760 million adults by 2050. 

 

"Achieve-1 is the first of seven Phase 3 studies examining the safety and efficacy of orforglipron across people with diabetes and obesity. We are pleased to see that our latest incretin medicine meets our expectations for safety and tolerability, glucose control and weight loss, and we look forward to additional data readouts later this year," said David A Ricks, Lilly chair and CEO. "As a convenient once-daily pill, orforglipron may provide a new option and, if approved, could be readily manufactured and launched at scale for use by people around the world."

 

In the first Phase 3 trial of the Achieve programme, orforglipron met the primary endpoint of superior A1C reduction compared to placebo at 40 weeks, lowering A1C by an average of 1.3% to 1.6% from a baseline of 8.0%, using the efficacy estimand. In a key secondary endpoint, more than 65% of participants taking the highest dose of orforglipron achieved an A1C less than or equal to 6.5%, which is below the American Diabetes Association's (ADA) defined threshold for diabetes. In an additional key secondary endpoint, participants taking orforglipron lost an average of 16.0 lbs (7.9%) at the highest dose. Given that participants had not yet reached a weight plateau at the time the study ended, it appears that full weight reduction was not yet attained, a statement said. 

 

For the treatment-regimen estimand, each dose of orforglipron led to statistically significant A1C reductions. In the key secondary endpoint for body weight, 12 mg and 36 mg doses led to statistically significant reductions.

 

• A1C reduction: 1.2% (3 mg), 1.5% (12 mg), 1.5% (36 mg), 0.4% (placebo)

• Percent weight reduction: 4.5% (3 mg), 5.8% (12 mg), 7.6% (36 mg), 1.7% (placebo)

• Weight reduction: 4.2 kg (9.3 lbs; 3 mg), 5.2 kg (11.5 lbs; 12 mg), 7.2 kg (15.8 lbs; 36 mg), 1.5 kg (3.4 lbs; placebo)

 

The overall safety profile of orforglipron in Achieve-1 was consistent with the established GLP-1 class. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity. The most common adverse events for participants treated with orforglipron were diarrhea, nausea, dyspepsia and vomiting. Overall treatment discontinuation rates due to adverse events were 6% and 8% for orforglipron. No hepatic safety signal was observed, it said. -TradeArabia News Service