Eli Lilly And Co (NYSE:LLY) stock is trading higher on Thursday after the U.S. healthcare giant reported topline Phase 3 results from ACHIEVE-1 trial of orforglipron compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone.

Eli Lilly adds that 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. 

The trial randomized 559 participants to receive either 3 mg, 12 mg, or 36 mg orforglipron or placebo.

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Lilly said on Thursday that it expects to submit orforglipron for weight management to global regulatory agencies by the end of this year, with the submission for the treatment of type 2 diabetes anticipated in 2026. 

In the first Phase 3 trial of the ACHIEVE program, orforglipron met the primary endpoint of superior A1C (blood sugar) 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%, below the American Diabetes Association’s 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 when the study ended, it appears that full weight reduction had not yet been attained.

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.

The most common adverse events for participants treated with orforglipron (3 mg, 12 mg, and 36 mg, respectively) were diarrhea (19%, 21%, and 26%) vs. 9% with placebo, nausea (13%, 18% and 16%) vs. 2% with placebo, dyspepsia (10%, 20% and 15%) vs. 7% with placebo, constipation (8%, 17% and 14%) vs. 4% with placebo, and vomiting (5%, 7% and 14%) vs. 1% with placebo.

Overall treatment discontinuation rates due to adverse events were 6% (3 mg), 4% (12 mg), and 8% (36 mg) for orforglipron vs. 1% with placebo.

No hepatic safety signal was observed.

Pfizer Inc’s (NYSE:PFE) oral danuglipron was tied to “high rates” of mild gastrointestinal side effects, leading to more than half of the patients across all dose groups dropping out from the trial. 

More results from the ACHIEVE Phase 3 clinical trial program will be shared later this year, along with findings from the ATTAIN Phase 3 clinical trial program evaluating orforglipron for weight management.

Price Action: LLY stock is up 11.3% at $817.99 during the premarket session at the last check Thursday.

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