IMMUNOLOGY lebrikizumab SC

Eli Lilly

Proposed Indications

Moderate to severe atopic dermatitis (AD)

Clinical Overview

Lebrikizumab is an interleukin-13 (IL-13) inhibitor.

The double-blind, placebo-controlled, phase 3 ADvocate 1 (NCT04146363; n=424) and Advocate 2 (NCT04178967; n=472) trials evaluated lebrikizumab monotherapy in patients ages ≥ 12 years (weighing ≥ 40 kg) with moderate to severe AD. Patients were randomized 2:1 to lebrikizumab 500 mg SC initially and at 2 weeks, followed by lebrikizumab 250 mg SC or placebo every 2 weeks. Co-primary endpoints in each trial were an IGA of 0 or 1 (clear or almost clear skin) with a reduction of ≥ 2 points from baseline and EASI-75. In both trials at week 16, significantly more patients on lebrikizumab achieved the IGA endpoint compared to those given placebo (ADvocate 1: 43.1% versus 12.7%, respectively; ADvocate 2: 33.2% versus 10.8%, respectively; p<0.001 for both). Similarly, lebrikizumab led to higher rates of EASI-75 response at week 16 (ADvocate 1: 58.8% versus 16.2%, respectively; ADvocate 2: 52.1% versus 18.1%, respectively; p<0.001 for both). Significant improvements in skin clearing and itching were seen as early as week 4. At week 16, patients who responded to lebrikizumab were re-randomized to lebrikizumab 250 mg every 2 weeks or every 4 weeks or placebo for an additional 36 weeks. At week 52, the studies demonstrated similar and durable responses with lebrikizumab given every 2 and every 4 weeks (IGA 0/1 response rate: ADvocate 1, 76% versus 74%, respectively, and ADvocate 2, 65% versus 81%, respectively; EASI-75 response rate: ADvocate 1, 79% versus 79%, respectively, and ADvocate 2, 77% versus 85%, respectively). Lebrikizumab was well tolerated. The most common TEAEs were conjunctivitis, nasopharyngitis, and headache.

The double-blind, parallel-group, phase 3 ADhere trial (NCT0425033; n=211) evaluated every-2-week SC dosing (after an initial loading dose) of lebrikizumab in combination with a topical corticosteroid (TCS) compared to TCS therapy alone in patients ages ≥ 12 years (weighing ≥ 40 kg) with moderate to severe AD. Medium potency (triamcinolone 0.1%) and low potency (hydrocortisone 1%) TCS creams were used in the study. The patients could taper, stop, and resume TCS therapy as needed. At week 16, significantly more patients achieved an IGA of 0/1 and EASI-75 (co-primary endpoints) in the lebrikizumab/TCS group compared to the placebo/TCS group (IGA 0/1: 41.2% versus 22.1%, respectively [p=0.01]; EASI-75: 69.5% versus 42.2%, respectively [p<0.001]). Lebrikizumab plus a TCS was well tolerated.

Place In Therapy

AD affects an estimated 31.6 million people in the US, including 9.6 million children and adolescents. Approximately 30% and 40% of cases in pediatrics and adults, respectively, are moderate to severe. The onset of AD occurs before age 6 years in about 80% of cases. While several systemic DMTs are available to treat moderate and severe AD, topical emollients, corticosteroids, and immunomodulators remain important options for treating AD; however, long-term continuous use of TCSs and immunomodulators is limited by TEAEs.

If approved, lebrikizumab will be the second biologic for AD that solely targets IL-13, following tralokinumab’s (Adbry™) approval in December 2021 for use in adults only. Lebrikizumab will compete with tralokinumab and dupilumab (Dupixent®). Dupilumab inhibits IL-4 and IL-13 signaling and is indicated for moderate to severe AD in patients ≥ 6 months of age. Lebrikizumab, tralokinumab, and dupilumab have similar maintenance dosing regimens (every 2 or 4 weeks). Non-comparative clinical trials report greater responses with lebrikizumab monotherapy (IGA difference from placebo range, 22% and 30%; EASI-75 difference from placebo range, 43% and 33%) compared to tralokinumab monotherapy (IGA difference from placebo range, 9% to 12%; EASI-75 difference from placebo range, 12% to 22%). Similar responses were reported in non-comparative trials with lebrikizumab and dupilumab (dupilumab IGA difference from placebo, 28%; EASI-75 difference from placebo range, 32% to 36%).

FDA APPROVAL TIMELINE

September 2023

 Fast Track

FINANCIAL FORECAST (reported in millions)