- 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
MENLO PARK, Calif., Jan. 31, 2018 (GLOBE NEWSWIRE) -- Dermira, Inc. (NASDAQ:DERM), 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, today announced the initiation of a Phase 2b dose-ranging study evaluating the safety and efficacy of lebrikizumab in adult patients with moderate-to-severe atopic dermatitis, the most common form of eczema. 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.
“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 Dermira. “Based on compelling Phase 2 proof-of-concept data in moderate-to-severe atopic dermatitis patients, we look forward to further evaluating lebrikizumab. We believe the Phase 2b dose-ranging study, with the introduction of a loading dose, as well as higher dosing regimens, will allow us to optimize the clinical profile of lebrikizumab in patients living with this debilitating condition.”
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 the United States. The study will evaluate three active treatment groups compared to a placebo treatment group, for 16 weeks, with patients randomized in a 3:3:3:2 fashion:
- Treatment Group 1: A loading dose of 250 mg of lebrikizumab at week 0, followed by 125 mg of lebrikizumab every four weeks.
- Treatment Group 2: A loading dose of 500 mg of lebrikizumab at week 0, followed by 250 mg of lebrikizumab every four weeks.
- Treatment Group 3: 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 Group 4: 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
In January 2018, results from the TREBLE study were accepted and published online in the Journal of the American Academy of Dermatology. TREBLE was a randomized, placebo-controlled, double-blind, Phase 2, proof-of-concept study designed to assess the efficacy and safety of lebrikizumab as add-on therapy to twice daily topical corticosteroids (TCS) for adult patients with moderate-to-severe atopic dermatitis. The study was conducted by F. Hoffmann-La Roche Ltd.
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 U.S. Food and Drug Administration for the treatment of primary axillary hyperhidrosis (excessive underarm sweating beyond what is needed for normal body temperature regulation); olumacostat glasaretil (formerly DRM01), in Phase 3 development for the treatment of acne vulgaris; and lebrikizumab, in Phase 2b development for the treatment of moderate-to-severe atopic dermatitis. Dermira is headquartered in Menlo Park, Calif. For more information, please visit http://www.dermira.com. Follow @DermiraInc on Twitter and LinkedIn.
In addition to filings with the Securities and Exchange Commission (SEC), press releases, public conference calls and webcasts, Dermira uses its website (www.dermira.com), LinkedIn page (https://www.linkedin.com/company/dermira-inc) and corporate Twitter account (@DermiraInc) as channels of distribution of information about its company, product candidates, planned financial and other announcements, attendance at upcoming investor and industry conferences and other matters. Such information may be deemed material information and Dermira may use these channels to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor Dermira’s website, LinkedIn page and Twitter account in addition to following its SEC filings, press releases, public conference calls and webcasts.
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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Ian Clements, Ph.D.
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Robert H. Uhl