Lebrikizumab Safe, Effective Against Moderate-to-Severe Eczema in Mid-Stage Trial

By Marilynn Larkin

March 04, 2020

NEW YORK (Reuters Health) - The monoclonal antibody lebrikizumab was effective and generally well tolerated in adults with moderate-to-severe atopic dermatitis, a dose-ranging study reveals.

The investigational agent, with the trade name Dermira, was fast-tracked by the U.S. Food and Drug Administration in December 2019 for atopic dermatitis.

"This is a very exciting time for our adult and pediatric patients with eczema and beyond," Dr. Emma Guttman-Yassky of the Icahn School of Medicine at Mount Sinai in New York City told Reuters Health by email. "The treatment options for eczema are expanding to include narrow treatments, such as lebrikizumab, which targets only a single immune molecule, interleukin 13. With a single target, patients show high level of treatment success, and durability of response."

For the 16-week phase 2b study, Dr. Guttman-Yassky and colleagues randomly assigned 280 patients (mean age, 39; 59% women) to receive either placebo every two weeks, or subcutaneous injections of lebrikizumab at 125 mg every four weeks; 250 mg every four weeks; or 250 mg every two weeks.

The primary end point was the percentage change from baseline in the Eczema Area and Severity Index (EASI). Secondary end points included the percentage change in the pruritus numeric rating scale (NRS) score and a pruritus NRS score improvement of at least four points.

As reported in JAMA Dermatology, compared with placebo (EASI percentage change, −41.1%), lebrikizumab groups showed dose-dependent, statistically significant improvement in the primary end point: −62.3% for 125 mg every four weeks; −69.2% for 250mg every four weeks, and −72.1% for 250mg every two weeks.

Pruritus NRS improvement of at least four points was seen as early as day 2 in the high-dose lebrikizumab group (9 of 59; 15.3%), compared to 2 of 44 (4.5%) for placebo-treated patients.

Treatment-emergent adverse events were reported in 46.2% of placebo patients, versus 57.5% for lebrikizumab at 125 mg/four weeks; 48.8% for 250 mg/four weeks, and 61.3% for 250 mg/two weeks. Most events were mild-to-moderate and did not lead to discontinuation.

Specifically, low rates were reported for injection-site reactions (1.9% in the placebo group vs. 5.7% in all lebrikizumab groups), herpes virus infections (3.8% vs. 3.5%), and conjunctivitis (0% vs. 2.6%).

Dr. Guttman-Yassky said, "This treatment can provide additional benefit on existing treatments for our patients with eczema, and with very good safety. The next step is a large phase 3 (trial) that is underway to ultimately provide patients with atopic dermatitis a novel, targeted treatment."

Dr. Holly Kanavy, a dermatologist at Montefiore Medical Center in New York City, commented in an email to Reuters Health, "These results are very promising and will offer a great treatment option for many of our patients suffering with this potentially debilitating disease."

"Improvement in itch is particularly exciting, since this is a huge burden for many of our patients," she said. "In this study, relief was experienced by many patients as early as the second day of treatment. I have seen firsthand how life-altering it is when the itching stops for these patients. Many of them are able to sleep through the night for the first time in years."

"The safety profile is reassuring as well, and is on par with other biologics targeting the IL-4/13 pathway," she said.

"Lebrikizumab may offer an alternative to those who don't respond adequately to dupixent, an IL-4 receptor alpha-antagonist that inhibits IL-4 and IL-13 signaling and has been approved in Europe and the US for the treatment of adolescents and adults with moderate-to-severe atopic dermatitis," she noted. "Lebrikizumab may also offer a more convenient dosing schedule, with a possible Q4- week dosing regimen."

That said, she added, "The study only lasted for 16 weeks, so additional studies will be needed to evaluate for maintenance of response over time for different dosing regimens. It will also be important to assess for efficacy, safety, and tolerability in children and adolescents."

The study was supported and funded by Dermira, Inc.

SOURCE: http://bit.ly/2wpamTZ JAMA Dermatology, online February 26, 2020.