Eli Lilly Reports Positive Phase 3 Results for Three Drug Programs

Eli Lilly announced positive, topline results from the Phase 3 ADorable-1 trial evaluating the safety and efficacy of EBGLYSS (lebrikizumab-lbkz) in pediatric patients with moderate-to-severe atopic dermatitis. EBGLYSS met the primary and key secondary endpoints at Week 16, improving disease severity while delivering skin clearance and relief from persistent itch.

Atopic dermatitis is more common in children than adults, affecting 9.6 million children in the U.S., one-third of whom have moderate-to-severe disease. In the Phase 3 ADorable-1 study, 63 percent of patients achieved meaningful skin improvement (EASI-75) and 44 percent achieved clear or almost clear skin (IGA 0,1) at Week 16. In key secondary endpoints, 39 percent of patients achieved a high bar of near-complete skin clearance (EASI-90) and 35 percent achieved significant itch relief (Pruritus NRS =4-point improvement).

The safety and tolerability profile of EBGLYSS was consistent with adult and adolescent studies, with no injection site pain reported. EBGLYSS is an interleukin-13 (IL-13) inhibitor that selectively blocks IL-13 signaling with high binding affinity and slow dissociation rate. The cytokine IL-13 is a primary cytokine in atopic dermatitis.

In ADorable-1, participants were randomized to receive placebo or a weight-based dose of EBGLYSS. Topical corticosteroids were required beginning two weeks before randomization and throughout the 16-week study but could be decreased or stopped once patients achieved IGA 2 or less. The co-primary endpoints in ADorable-1 were EASI-75 and IGA 0,1 at Week 16.

Separately, Lilly's GLP-1 pill orforglipron was associated with greater weight loss and reductions in blood sugar levels than Novo Nordisk's rival drug Rybelsus in a head-to-head trial in people with diabetes. Lilly's trial enrolled nearly 1,700 people with diabetes whose blood sugar isn't under control with the old pill metformin. Patients were randomized into four equal groups. Two cohorts got either 7 milligram or 14 milligram doses of semaglutide, the active ingredient in Rybelsus. The rest got 12 milligram or 36 milligram doses of orforglipron.

Investigators compared how effectively the high and low doses of each medicine lowered blood sugar levels over the course of a year, first measuring for statistical "non-inferiority" and then "superiority." The orforglipron doses passed both thresholds. The high dose of Lilly's drug lowered blood sugar by an average of 1.9 percentage points, versus 1.5 percentage points for high-dose Rybelsus. A lower dose of orforglipron was also superior, pushing blood sugar down 1.7 percentage points compared to 1.2 percentage points for lower-dose Rybelsus.

Weight loss also favored Lilly's drug. The high doses of the two medications spurred weight loss of 8.2% and 5.3%, respectively, at 52 weeks. The lower-dose weight loss totals were 6.1% and 3.9%. Among orforglipron recipients, 9.7% and 8.7% in the high- and low-dose arms, respectively, discontinued treatment because of side effects, compared to rates of 4.9% and 4.5% in the Rybelsus arms.

Lilly said it plans to ask the FDA later this year to approve orforglipron in diabetes. Lilly expects the Food and Drug Administration to decide whether to clear use of orforglipron in obesity sometime in the second quarter.

In oncology, Eli Lilly reported that Retevmo met the primary endpoint in the LIBRETTO-432 study. Topline data showed a statistically significant and clinically meaningful improvement in event-free survival when selpercatinib was used as adjuvant therapy in patients with early-stage non-small cell lung cancer whose tumors carry a RET fusion and who had previously undergone initial therapy such as surgery. The global trial enrolled 151 patients and compared the twice-daily oral therapy against placebo.

Retevmo is already available in the U.S. for adults with RET fusion-positive NSCLC. Lilly noted that initial overall survival findings, a secondary endpoint, showed a trend favoring Retevmo, but the data were too immature to draw definitive conclusions. Lilly said the safety profile observed in LIBRETTO-432 was consistent with prior data from the drug's development program. The company plans to engage global health regulators on the results, present full data at a future medical event, and submit the findings to a peer-reviewed journal.