All three doses of Dermira, Inc.’s lebrikizumab showed greater improvements in the Eczema Area and Severity Index in a new Phase 2b dose-ranging study of adults with moderate-to-severe atopic dermatitis, and shares of Dermira, Inc. skyrocketed in premarket trading after the company announced these results.
Lebrikizumab is a novel, humanized monoclonal antibody designed to bind IL-13 with high affinity, specifically preventing the formation of the IL-13Rα1/IL-4Rα heterodimer complex, which inhibits downstream signaling.IL-13 is a central pathogenic mediator that drives multiple aspects of the pathophysiology of atopic dermatitis by promoting type 2 inflammation and mediating its effects on tissue, resulting in skin barrier dysfunction, itch, skin thickening and infection.
Following an end-of-phase 2 meeting with the U.S. Food and Drug Administration, Dermira plans to initiate a Phase 3 clinical development program for lebrikizumab by the end of 2019.
“These data are incredibly compelling and further demonstrate clinically that IL-13 is a key mediator in atopic dermatitis,” says Emma Guttman-Yassky, MD, PhD, The Sol and Clara Kest Professor, Vice Chair for Research in the Department of Dermatology, Director of the Center of Excellence in Eczema at Icahn School of Medicine at Mount Sinai and one of the lead investigators, in a news release. “I have many patients for which current therapies do not adequately address their needs. These data show that lebrikizumab may offer a targeted and well-tolerated therapeutic approach with high efficacy.”
Lebrikizumab Phase 2b Study Results
Each of the lebrikizumab doses evaluated showed a dose-dependent and statistically significant improvement in the primary endpoint, the mean percent change in EASI score from baseline to week 16. The improvement in EASI score was 62.3 percent for patients receiving lebrikizumab, 125 milligrams (mg), every four weeks (p=0.0165), 69.2 percent for patients receiving lebrikizumab, 250 mg, every four weeks (p=0.0022) and 72.1 percent for patients receiving lebrikizumab, 250 mg, every two weeks (p=0.0005) compared to 41.1 percent for patients receiving placebo.
Patients treated with lebrikizumab at the 250 mg dose every two or four weeks achieved statistically significant improvements in several other key efficacy measures compared to placebo after 16 weeks of treatment, including:
Lebrikizumab 250 mg every four weeks:
• 33.7 percent of lebrikizumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an investigator's global assessment (IGA) score of 0 or 1,compared to 15.3 percent with placebo (p=0.0392).
• 56.1 percent of lebrikizumab treated patients achieved a reduction of at least 75 percent from baseline in EASI score (EASI-75), compared to 24.3 percent on placebo (p=0.0021).
• 36.1 percent of lebrikizumab treated patients achieved a reduction of at least 90 percent from baseline in EASI score (EASI-90), compared to 11.4 percent on placebo (p=0.0062).
Lebrikizumab 250 mg every two weeks:
• 44.6 percent of lebrikizumab-treated patients achieved clearing or near-clearing of skin lesions, as measured by an IGA score of 0 or 1, compared to 15.3 percent with placebo (p=0.0023).
• 60.6 percent of lebrikizumab treated patients achieved a reduction of at least 75 percent from baseline in EASI-75, compared to 24.3 percent on placebo (p=0.0005).
• 44.0 percent of lebrikizumab treated patients achieved a reduction of at least 90 percent from baseline in EASI-90, compared to 11.4 percent on placebo (p=0.0006).
The secondary endpoints for the 125 mg lebrikizumab dosing arm did not meet statistical significance.
Moreover, the safety profile for lebrikizumab observed in the study was consistent with prior studies evaluating this investigational therapy.
The most common adverse events reported across all three lebrikizumab dosing arms were upper respiratory tract infection (7.5 percent vs. 5.8 percent for placebo), nasopharyngitis (6.6 percent vs. 3.8 percent for placebo), headache (3.1 percent vs. 5.8 percent for placebo) and injection site pain (3.1 percent vs. 1.9 percent for placebo). Conjunctivitis rates (2.6 percent compared to no reports in the placebo arm) and herpes infections (2.2 percent compared to no reports in the placebo arm) were low. Overall, adverse events observed in lebrikizumab-treated patients were primarily mild to moderate in severity and infrequently led to study discontinuation.
“Based on the compelling clinical profile observed in this study, we believe we have a potential best-in-disease therapy,” adds Tom Wiggans, chairman and chief executive officer of Dermira. “We intend to move quickly into a Phase 3 program following discussions with U.S. regulators.”
More on the Lebrikizumab Phase 2b Study
The randomized, double-blind, placebo-controlled, parallel-group Phase 2b study was designed to evaluate the safety and efficacy of lebrikizumab as monotherapy compared with placebo and to establish the dosing regimen for a potential Phase 3 program in patients with moderate-to-severe atopic dermatitis. The study enrolled 280 patients ages 18 years and older with moderate-to-severe atopic dermatitis at 57 sites in the United States. The study is evaluating three different lebrikizumab treatment dosing arms compared to a placebo arm, with patients randomized in a 3:3:3:2 fashion:
• Group 1: A loading dose of 250 mg of lebrikizumab at week 0, followed by 125 mg of lebrikizumab every four weeks.
• Group 2: A loading dose of 500 mg of lebrikizumab at week 0, followed by 250 mg of lebrikizumab every four weeks.
• Group 3: A loading dose of 500 mg of lebrikizumab at weeks 0 and 2, followed by 250 mg of lebrikizumab every two weeks.
• Group 4: Placebo at week 0 and every two weeks thereafter.
The inclusion criteria for patients enrolled in this study included chronic atopic dermatitis for at least one year, an EASI score of 16 or greater, an IGA score of 3 or greater, and a body surface area involving at least 10 percent at screening and baseline. Following the end of the 16-week assessment period, patients are followed for an additional 16 weeks.