Eli Lilly and Co. (NYSE:LLY) on Tuesday released topline results from the Phase 3 ATTAIN-2 trial, evaluating oral orforglipron in adults with obesity or overweight and type 2 diabetes.
In the trial, all three doses of orforglipron met the primary and all key secondary endpoints, delivering significant weight loss, meaningful A1C reductions, and improvements in cardiometabolic risk factors at 72 weeks.
With the completion of ATTAIN-2, Lilly now has the complete clinical data package required to initiate global regulatory submissions for orforglipron.
In the ATTAIN-2 trial, orforglipron met the primary endpoint of superior body weight reduction compared to placebo.
Earlier this month, Eli Lilly stock came under pressure when it released data from Phase 3 ATTAIN-1 trial, showing orforglipron 36 mg lowered weight by an average of 12.4% (27.3 lbs) compared to 0.9% (2.2 lbs) with placebo using the efficacy estimand, below Wall Street’s expectations of around 15%.
Tuesday’s data helped ease some of those concerns, with shares rising nearly 3% in premarket trading.
For the primary endpoint, daily orforglipron 36 mg lowered weight by an average of 10.5% (22.9 lbs) compared to 2.2% (5.1 lbs) with placebo using the efficacy estimand.
In a key secondary endpoint, orforglipron lowered A1C (blood sugar) by 1.3% to 1.8% from a baseline of 8.1% across doses.
In another key secondary endpoint, 75% of participants taking the highest dose of orforglipron achieved an A1C ≤6.5%, at or below the American Diabetes Association’s definition of diabetes.
Additionally, orforglipron showed clinically meaningful benefits across key cardiovascular risk factors, including non-HDL cholesterol, systolic blood pressure, and triglycerides.
In a pre-specified exploratory analysis, the highest dose of orforglipron reduced high-sensitivity C-reactive protein (hsCRP) levels, a marker of inflammation, by 50.6%.
In the treatment regimen estimand, orforglipron demonstrated statistically significant improvements across both the primary and all key secondary endpoints when compared with placebo.
Participants on orforglipron achieved meaningful reductions in body weight, with average declines of 5.1% at the 6 mg dose, 7.0% at 12 mg, and 9.6% at 36 mg, versus 2.5% for placebo.
The proportion of patients achieving at least a 10% reduction in body weight rose with dosage, reaching 22.6% for 6 mg, 31.2% for 12 mg, and 45.6% for 36 mg, compared with just 9.0% in the placebo group.
Similarly, those achieving weight reductions of at least 15% were 6.8%, 14.4%, and 26.0% across the three dose levels, versus 3.0% on placebo.
Glycemic control also improved markedly, with reductions in A1C of 1.2%, 1.5%, and 1.7% across the 6 mg, 12 mg, and 36 mg groups, compared with 0.5% for placebo.
Among participants, 64.6% (6 mg), 75.9% (12 mg), and 75.5% (36 mg) achieved an A1C level below 7%, versus 30.5% with placebo. Furthermore, 52.5%, 57.6%, and 66.6% of patients in the respective treatment groups reached an A1C of 6.5% or lower, compared with only 15.4% in the placebo arm.
The safety profile of orforglipron in ATTAIN-2 was consistent with the established GLP-1 receptor agonist 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 (6 mg, 12 mg and 36 mg, respectively) were nausea (20.1%, 31.1% and 36.4%) vs. 8.4% with placebo, vomiting (12.8%, 20.2% and 23.1%) vs. 3.8%, diarrhea (21.3%, 24.8% and 27.4%) vs. 15.0%, constipation (17.7%, 21.1% and 22.4%) vs. 7.8%, and dyspepsia (9.1%, 15.4% and 10.9%) vs. 3.5%.
Treatment discontinuation rates due to adverse events were 6.1% (6 mg), 10.6% (12 mg), and 10.6% (36 mg) for orforglipron vs. 4.6% with placebo.
Price Action: LLY stock is trading higher by 2.72% to $714.22 premarket at last check Tuesday.
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