Eli Lilly's Orforglipron Achieves 12.4% Weight Loss in Phase 3 Trial, Global Launch Planned

Eli Lilly and Company revealed promising top-line outcomes from its Phase 3 ATTAIN-1 clinical trial for orforglipron, an investigational oral GLP-1 (glucagon-like peptide-1) receptor agonist, in adults with obesity or overweight and associated medical conditions, excluding diabetes. The investigational drug demonstrated robust efficacy in promoting weight loss across its various dosages, maintaining a safety and tolerability profile similar to injectable GLP-1 therapies over a 72-week period. These results have positioned Lilly to submit orforglipron for regulatory approval globally by the end of the year and to prepare for its anticipated launch.

Orforglipron, a once-daily oral pill, showed significant reductions in body weight, meeting both primary and secondary endpoints in the trial. Participants administered with the highest dose of 36 mg displayed an average weight reduction of 12.4%, equating to 27.3 pounds. The placebo group, in contrast, achieved a mere 0.9% weight loss. Furthermore, 59.6% of participants on the highest dose achieved a weight reduction of 10% or more, with 39.6% losing at least 15% of body weight. Additional analyses confirmed significant reductions in cardiovascular risk markers, including non-HDL cholesterol, triglycerides, and systolic blood pressure across all dosage groups. Notably, a 47.7% reduction in high-sensitivity C-reactive protein (hsCRP) levels was observed with the highest dose.

Eli Lilly's executive vice president and president of Lilly Cardiometabolic Health, Kenneth Custer, Ph.D., emphasized the transformative potential of orforglipron in obesity care, offering a convenient oral alternative to injectable treatments. He underscored the company's commitment to addressing the critical global health challenge posed by obesity, which affects more than a billion people worldwide.

The ATTAIN-1 trial involved 3,127 participants and employed a randomized, double-blind, placebo-controlled design. Participants, spanning diverse regions including the U.S., Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain, and Taiwan, were administered either 6 mg, 12 mg, or 36 mg doses of orforglipron or placebo. The trial's main objective was to demonstrate orforglipron's superiority to placebo in reducing body weight from the baseline over a 72-week period for individuals with a BMI of 30 kg/m² or higher, or a BMI of 27 kg/m² or higher with associated comorbidities.

Safety data from the trial indicated that the adverse event profile was consistent with known effects of GLP-1 receptor agonists, mostly gastrointestinal in nature and ranging from mild to moderate severity. Common adverse events included nausea, constipation, diarrhea, vomiting, and dyspepsia, with the rates higher in the orforglipron groups compared to placebo. While treatment discontinuation due to adverse events occurred in 5.1% to 10.3% of participants depending on the dose, the overall discontinuation rate was lower compared to placebo. Importantly, no hepatic safety signals emerged during the trial.

Lilly plans to present further details of the ATTAIN-1 trial next month at the European Association for the Study of Diabetes Annual Meeting and publish them in a peer-reviewed journal. Additional results are anticipated later in the year, including data from the ACHIEVE Phase 3 trial program, which is exploring orforglipron as a treatment for adults with type 2 diabetes.

The investigational drug orforglipron is distinguished as a small molecule rather than a peptide, allowing it to be administered without food or water restrictions. Originally discovered by Chugai Pharmaceutical Co., Ltd. and later licensed by Lilly, orforglipron's development has been a collaborative effort between the two entities. Eli Lilly is conducting ongoing Phase 3 studies targeting type 2 diabetes and weight management in adults with obesity or overweight presenting with weight-related medical problems.

Orforglipron's entry into the market is expected to add a needle-free option to the multi-billion-dollar weight-loss drug industry, currently dominated by injectable treatments like Mounjaro, Wegovy, and Ozempic. Although the weight-loss efficacy of the pill is slightly less than its injectable counterparts, analysts predict a significant market demand driven by the convenience of oral administration. Obesity specialists also hope that the cost will be lower than injectables, potentially making it accessible to a broader population.

As Lilly gears up for submission of orforglipron for licensing, the company anticipates an extensive global launch to address the urgent public health need posed by obesity and its associated health challenges.