Peter Lio, MD

Several data points for lebrikizumab (EBGLYSS; Lilly), a monoclonal antibody targeting interleukin-13, were reported at the 2025 American Academy of Dermatology (AAD) meeting held in Orlando, Florida earlier this month.¹

The injectable medicine is approved to treat adults and adolescents aged 12 years and older with moderate-to-severe atopic dermatitis (AD), who weigh less than 88 lbs (40 kg).²

Peter Lio, MD, a clinical assistant professor of Dermatology & Pediatrics at Northwestern University Feinberg School of Medicine, a Fellow of the American Academy of Dermatology, and a Diplomate of the American Board of Dermatology (board-certified in Dermatology), highlighted and explained key data points in this Q+A interview with Contemporary Pediatrics.³

Below, you'll find key data points presented for lebrikizumab, followed by commentary from Lio, further explaining the data and potential implications on the pediatric population, impacted by atopic dermatitis (AD).

Lebrikizumab improves atopic dermatitis symptoms in patients previously on dupilumab

One study presented at AAD demonstrated that lebrikizumab improves itch, sleep interference, and skin pain in patients with moderate-to-severe AD who were were previously treated with dupilumab (Dupixent; Sanofi and Regeneron).¹

The study, ADapt (NCT05369403), was an open-label, 24-week trial that evaluated the efficacy of lebrikizumab in adults and adolescents who discontinued dupilumab due to inadequate response, intolerance, or other reasons.

"The proportions of patients achieving Pruritus Numeric Rating Scale (PNRS) ≥3-point improvement were 72.9% and 77.5% observed, respectively," according to the study authors. The proportion of patients reaching ≥4-point PNRS improvement also increased over time, with 53.2% at week 16 and 61.5% at week 24.

Click here for full study results, previously covered by Contemporary Pediatrics.

Sleep interference, a key concern for AD patients, also improved. The study reported that "Sleep-Loss Scale ≥2-point improvement was achieved by 41.7% and 42.1% of patients at weeks 16 and 24, respectively."

Additionally, skin pain, as assessed by the Skin Pain Numeric Rating Scale (NRS), showed significant improvement, with 58.8% of patients achieving at least a 4-point reduction at week 16 and 75.0% at week 24.

Peter Lio, MD:

The ADapt study was conducted in patients previously exposed to dupilumab. Interestingly, more than 40% of these patients had been on 2 or more systemic agents. The focus was on patient reported outcomes (itch and sleep improvements) in this refractory patient population, showing levels of improvement similar to what was seen in the pivotal studies.

This is exciting because many clinicians want to know what to expect for patients who have previously been on dupilumab, and this gives us some reassuring evidence in this important population.

Contemporary Pediatrics:

Can you explain the amount of itch reduction observed and what this might mean for quality of life, specifically for the adolescent patients?

Lio:

The ADapt trial enrolled adults and adolescent patients, with ages 12-17 years making up 10.5%. The disclosure reports clinically meaningful measures, including at least 3- and 4-point improvement in itch NRS score, 2-point improvement in sleep disturbance due to itch and 4-point improvement in skin pain.

Lebrikizumab provided a clinically-meaningful improvement in itch response in at least half of patients who discontinued dupilumab for inadequate response.

These improvements in sleep and pain are impressive and my sense is that these are 2 of the most important factors for quality of life, resulting in meaningful improvements.

Phase 3b ADmirable study (NCT05372419)

The objective in this trial was to highlight 16-week results for the patient-reported measures of itch and itch interference on sleep from the 24-week study, the first to evaluate the safety and efficacy of lebrikizumab in adult and adolescent patients with skin of color and moderate-to-severe AD, according to authors of the study abstract.⁴

Additionally, investigators reported 16-week results for patient-reported measures of skin pain from lebrikizumab adult and adolescent patients with skin of color and moderate-to-severe AD.

In the study, lebrikizumab 500-mg loading dose was administered at baseline and week 2, then 250 mg every 2 weeks.

At baseline (n = 90), 70 (90%), 59 (76%), and 47 (60%) reported Pruritus NRS ≥4, Skin Pain NRS ≥4, and Sleep-Loss Scale ≥2, respectively, according to the study abstract. At week 16, the proportion of patients with pruritus NRS ≥3-point and ≥4-point improvement were (as observed):

• 66.2% (43/65) and 58.1% (36/62), NRI/MI, 64.2% (47/73) and 55.4% (39/70), respectively

Skin Pain NRS ≥4-point improvement:

• 58.8% (30/51), NRI/MI, 57.4% (34/59)

Sleep-Loss Scale ≥2-point improvement:

• 30.8% (12/39), NRI/MI, 31.0% (15/47)

Sustained response with lebrikizumab up to 3 years

Also presented at AAD were data from the phase 3 monotherapy trials, ADvocate1, ADvocate2, and the long-term extension study ADjoin (NCT04392154), for sustained depth of response with lebrikizumab treatment up to 3 years.⁵

"Lebrikizumab responders at Week 16 (achieved ≥75% improvement in Eczema Area and Severity Index [EASI 75] or Investigator’s Global Assessment [IGA] of 0/1 without rescue therapy) who completed ADvocate1 and ADvocate2 (1 full year) and enrolled in ADjoin, received lebrikizumab 250 mg every 2 or 4 weeks (Q2W or Q4W) for an additional 2 years," wrote the study investigators.

According to a study abstract, authors noted that at week 100 of ADjoin, which is 3 years of lebrikizumab treatment, Investigator's Global Assessment (IGA) 0 was reported for 26 of 41 of patients receiving lebrikizumab every 2 weeks, and for 25 of 50 receiving the injection every 4 weeks.

"EASI 90/EASI 100 was reported for 79.4% [50/63]/49.2% [31/63] of patients receiving lebrikizumab Q2W; 86.8% [59/68]/50.0% [34/68] receiving lebrikizumab Q4W," according to results posted in the abstract.

Peter Lio, MD:

My major takeaways from the 3 year long-term results:

There was a deep, long-term response found for lebrikizumab for up to 3 years of continuous treatment. 8 out of 10 subjects achieved almost clear skin (as indicated by EASI 90) up to 3 years. Additionally, over 50% of the patients experienced total skin clearance, as assessed by EASI 100 or IGA (0).

From the ADmirable trial (lebrikizumab in skin of color patients):

The ADmirable study assessed lebrikizumab efficacy and safety in an under-studied patient population, patients with moderate-to-severe AD and skin of color. The preliminary data had been disclosed as AAD late-breaker last year, this year the disclosure focuses on patient reported outcomes and shows that lebrikizumab improves symptoms of itch, skin pain, and interference of itch on sleep after 16 weeks, consistently with what has been shown in the pivotal studies. This is the first trial in this patient population with results available.

My overall thoughts are that this is among the most robust data we have seen for any of the FDA-approved biologics, though the caveat is that you can't really directly compare between different trials, given all of the variables that are involved. That said, I am very excited by these robust results.

References:

1. Ebert M. Lebrikizumab improves atopic dermatitis symptoms in patients previously on dupilumab. Contemporary Pediatrics. March 7, 2025. Accessed March 27, 2025. https://www.contemporarypediatrics.com/view/lebrikizumab-improves-atopic-dermatitis-symptoms-in-patients-previously-on-dupilumab

2. Ebglyss (lebrikizumab-lbkz) indication. Lilly. Accessed March 27, 2025. https://ebglyss.lilly.com/

3. Peter A. Lio, MD. Providers. Medical Dermatology Associates of Chicago. Accessed March 27, 2025. https://www.dermchicago.com/provider/peter-a-lio-md

4. Alexis A, Moiin A, Waibel J, et al. Lebrikizumab improves itch, skin pain, and the interference of itch on sleep in adult and adolescent patients with moderate-to-severe atopic dermatitis and skin of color: 16-week results from the ADmirable study. Abstract. Presented at: The 2025 American Academy of Dermatology Annual Meeting. Orlando, Florida.

5. Simpson E, Biedermann T, Kircik L, et al. Raising the Bar of Efficacy in Atopic Dermatitis: Lebrikizumab Maintains Depth of Response Over 3 Years in Week 16 Responders. Abstract. Presented at: The 2025 American Academy of Dermatology Annual Meeting. Orlando, Florida.