麻豆传媒

Most patients with moderate-to-severe atopic dermatitis (AD) who received lebrikizumab (EBGLYSS) every 2 weeks maintained a favorable response to the drug out to the 1-year mark, recent trial data showed. Perhaps just as importantly, people receiving the drug every 4 weeks maintained a substantial response, suggesting less-frequent treatments are required over time compared with currently available therapeutics.

The findings came from two separate phase 3 trials, both of which were funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company, which manufactures lebrikizumab. The findings appeared in the .

Because of the drug's potential, in 2019 the FDA granted lebrikizumab for the treatment of moderate-to-severe AD in adults and adolescents. One found that as many as 73% of patients with AD experienced improvement or clearance after treatment with lebrikizumab.

Andrew Blauvelt, MD, MBA, a dermatologist and investigator at Oregon Medical Research Center, is the current paper's first author. He recently discussed the trial and its findings -- as well as lebrikizumab's prospects for FDA action in the near future -- with the Reading Room. The exchange has been edited for length and clarity.

This was a phase 3 trial for lebrikizumab, which has been shown to be safe and effective for people with AD. What was this trial designed to contribute to what we know about this drug?

Blauvelt: For AD treatment, existing biologics such as JAK inhibitors have helped achieve long-term disease control with an acceptable safety profile. However, a significant number of patients fail to achieve sustained long-term clinical benefit with these drugs, and safety issues become a concern in certain populations.

Lebrikizumab, a novel monoclonal antibody and IL-13 inhibitor, has thus far proven effective and safe over the longer term. This current paper describes results from the week 16 primary endpoint in the pivotal trials to week 52. More specifically, the manuscript details what happens to week 16 initial responders (dosed every 2 weeks from weeks 0-16) when they are placed on one of three maintenance doses from weeks 16-52: either continued dosing every 2 weeks, extended dosing to every 4 weeks, or going to placebo.

Thus, the trial was designed to identify the proper maintenance dosing frequency.

How would you summarize trial's key findings, and what was your reaction?

Blauvelt: Efficacy in patients with maintenance dosing every 2 weeks and every 4 weeks was similar.

This was surprising to us. We expected 2-week dosing to be better than 4-week dosing. However, surprising, it is indeed a good result for patients. It means they can maintain efficacy with doses only every 4 weeks, which is an improvement over dupilumab, which requires maintenance doses every 2 weeks for most patients.

Did anything else surprise you about the trial or its findings?

Blauvelt: It was also surprising that patients put on placebo "maintenance dosing" did well for long periods. There was no dramatic drop-off in efficacy when drug dosing was stopped at week 16. This suggests that lebrikizumab may be disease-modifying in some patients.

What was the drug's safety profile over the course of 1 year?

Blauvelt: Lebrikizumab was safe in most patients. Small percentages of patients (approximately 5%) can get conjunctivitis, but everything else looks great in terms of safety.

The drug received fast-track designation from the FDA in 2019. What are the potential next steps in that process?

Blauvelt: The drug is likely to be approved for moderate-to-severe AD by the FDA in the fall of 2023.

What is the key take-home message you would like dermatologists to be aware of in light of these findings specifically, and the present and future of lebrikizumab for AD treatment generally?

Blauvelt: Efficacy of lebrikizumab is at least comparable to efficacy of dupilumab for AD. By some measures, it is slightly better then dupilumab. Maintenance dosing every 4 weeks is a clear advantage of this drug over dupilumab.

Implications for practice

• Lebrikizumab (EBGLYSS) safe and effective for AD treatment after 1 year.
• Maintenance doses were effective at 4-week intervals rather than 2-week intervals, which is the standard for currently available treatments.
• FDA approval of lebrikizumab is anticipated this fall for treatment of moderate-to-severe eczema.