- Study expected to enroll approximately 275 patients
- Topline results expected in the first half of 2019
- TREBLE Phase 2 proof-of-concept results published in the
Journal of the American Academy of Dermatology
“Millions of people suffer from atopic dermatitis, and despite recent treatment advances, additional therapeutic options are needed to safely and effectively manage this chronic skin condition,” said Luis Peña, chief development officer of
Lebrikizumab Phase 2b Study
The randomized, double-blind, placebo-controlled, parallel-group Phase 2b study is designed to evaluate the safety and efficacy of lebrikizumab as a 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 is expected to enroll approximately 275 patients ages 18 years and older with moderate-to-severe atopic dermatitis at sites in
Treatment Group1: A loading dose of 250 mg of lebrikizumab at week 0, followed by 125 mg of lebrikizumab every four weeks.
Treatment Group2: A loading dose of 500 mg of lebrikizumab at week 0, followed by 250 mg of lebrikizumab every four weeks.
Treatment Group3: A loading dose of 500 mg of lebrikizumab at each of weeks 0 and 2, followed by 250 mg of lebrikizumab every two weeks. Treatment Group4: Placebo at week 0 and every two weeks thereafter.
The primary endpoint of the study is the percent change in the Eczema Area Severity Index (EASI) from baseline to week 16. Key secondary endpoints that will be evaluated during the 16-week treatment period include: the proportion of patients with a 75 percent improvement from baseline in EASI (EASI-75); the proportion of patients with an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and a reduction of 2 or more points (on a 5-point scale) from baseline; the proportion of patients achieving EASI-50 and EASI-90; and changes in sleep loss and pruritus (itch) scores from baseline, both scored using an 11-point numerical rating scale (NRS). Key inclusion criteria for patients enrolled in this study include 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 16-week treatment period, patients will be followed for an additional 16 weeks.
Lebrikizumab Phase 2 TREBLE Proof-of-Concept Study
Patients in the TREBLE study were randomized 1:1:1:1 to receive either a single, 125-mg dose of lebrikizumab plus TCS (n=52), a single, 250-mg dose of lebrikizumab plus TCS (n=53), 125 mg of lebrikizumab every four weeks plus TCS (n=51), or placebo every four weeks plus TCS (n=53), for up to 12 weeks. Patients in all treatment groups were required to receive two weeks of twice daily TCS treatment prior to baseline measurement and throughout the 12-week treatment period. The primary endpoint was the percentage of patients achieving EASI-50 at week 12.
After 12 weeks of treatment, significantly more patients achieved EASI-50 with lebrikizumab administered at 125 mg every four weeks (82.4%; p=0.026) compared with placebo (62.3%). Patients who received single dose lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo.
Lebrikizumab was generally well-tolerated. There were no imbalances in proportions of patients reporting adverse events (AEs), serious adverse events, events leading to discontinuation, or overall infections when comparing all lebrikizumab-treated patients with placebo. Three patients (2.0%) in the lebrikizumab groups (all doses combined) and one patient (2.0%) in the placebo group experienced an AE that led to withdrawal from the study. There were no deaths, anaphylactic reactions, malignancies, or protocol-defined parasitic or targeted intracellular infections of interest. Injection-site reactions occurred infrequently (1.3% in all lebrikizumab groups and 1.9% in the placebo group).
The dose-response relationships observed across multiple endpoints in TREBLE, as well as trends towards improved efficacy with increasing dose and duration, suggest that further increases in the dose and/or treatment duration may result in improved efficacy. Dermira’s Phase 2b study will evaluate this.
About Atopic Dermatitis
Atopic dermatitis is the most common and severe form of eczema, a chronic inflammatory condition that can present as early as childhood and continue into adulthood. A moderate-to-severe form of the disease is characterized by rashes on the skin that often cover much of the body and can include redness, cracking, dryness and intense, persistent itching. The skin condition can have a negative impact on patients’ mental and physical functioning, limiting their daily activities and health-related quality of life. Patients with moderate-to-severe atopic dermatitis have reported a larger impact on quality of life than patients with psoriasis.
Lebrikizumab is a novel, humanized monoclonal antibody designed to bind to IL-13 with high affinity, specifically preventing heterodimerization of the IL-13/IL-4 receptor and subsequent signaling. IL-13 plays a central role in type 2 inflammation and is an important pathogenic mediator in atopic dermatitis.
Dermira is a biopharmaceutical company dedicated to bringing biotech ingenuity to medical dermatology by delivering differentiated, new therapies to the millions of patients living with chronic skin conditions. Dermira is committed to understanding the needs of both patients and physicians and using its insight to identify and develop leading-edge medical dermatology programs. Dermira’s pipeline includes three late-stage product candidates that could have a profound impact on the lives of patients: glycopyrronium tosylate (formerly DRM04), for which a New Drug Application is under review by the
In addition to filings with the Securities and Exchange Commission (
The information in this press release contains forward-looking statements and information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. This press release contains forward-looking statements that involve substantial risks and uncertainties, including statements with respect to: Dermira’s goal of building a leading medical dermatology company dedicated to delivering differentiated, new therapies to the millions of patients living with chronic skin conditions; the description of and enrollment expectations for Dermira’s Phase 2b dose-ranging study of lebrikizumab for moderate-to-severe atopic dermatitis; the successful completion of, and timing expectations for the receipt and announcement of topline data from the Phase 2b dose-ranging study; the desired outcome of the Phase 2b dose-ranging study Dermira’s ability to optimize the clinical profile of lebrikizumab in patients living with atopic dermatitis; and a potential Phase 3 program to evaluate the safety and efficacy of lebrikizumab for the treatment of moderate-to-severe atopic dermatitis. These statements deal with future events and involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. Factors that could cause actual results to differ materially include risks and uncertainties such as those relating to the design, implementation and outcomes of Dermira’s clinical trials; Dermira’s dependence on third-party clinical research organizations, manufacturers and suppliers; and Dermira’s ability to continue to stay in compliance with applicable laws and regulations. You should refer to the section entitled “Risk Factors” set forth in Dermira’s Annual Report on Form 10-K, Dermira’s Quarterly Reports on Form 10-Q and other filings Dermira makes with the SEC from time to time for a discussion of important factors that may cause actual results to differ materially from those expressed or implied by Dermira’s forward-looking statements. Furthermore, such forward-looking statements speak only as of the date of this press release. Dermira undertakes no obligation to publicly update any forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.
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Vice President, Investor Relations
Source: Dermira, Inc.