Title

Olumacostat glasaretil (DRM01) for the treatment of acne vulgaris: Primary results from the DRM01-ACN02 phase 2b randomized controlled trial

Document Type

Conference Proceeding

Publication Date

6-1-2017

Publication Title

Journal of the American Academy of Dermatology

Abstract

Background: Sebum production, a critical factor in acne pathophysiology, is not addressed by available topical therapies. Olumacostat glasaretil (OG) inhibits acetyl coenzyme A carboxylase, a key regulator of the synthesis of sebum lipid components. This phase 2b trial assessed the safety and efficacy of OG gel in patients (pts) with facial acne vulgaris.

Methods: DRM01-ACN02 (NCT02431052) was a randomized, double-blind, vehicle (VEH)-controlled, dose-ranging, 12-week (wk) trial. Eligible pts were adults with facial acne vulgaris (≥20 inflammatory acne lesions [IALs], ≥20 non-inflammatory acne lesions [NIALs], and an Investigator Global Assessment [IGA] score of 3 or 4). Pts were randomized 2:2:2:1:1 to receive OG 4% once daily (QD), OG 7.5%-QD, OG 7.5% twice daily (BID), VEH-QD, or VEH-BID. Primary efficacy endpoints were IAL and NIAL counts, and IGA response rate (≥2-point improvement from baseline [BL]) at Wk12. MCMC multiple imputation was used to impute missing values in the ITT population. Significance was calculated vs combined VEH group using ANCOVA model (IAL, NIAL count) and Cochran-Mantel-Haenszel test (IGA response).

Results: 420 pts were randomized to receive OG 4%-QD, OG 7.5%-QD, OG 7.5%-BID, VEH-QD or VEH-BID; BL characteristics were similar. Significantly greater IAL and NIAL count reductions from BL were reported in OG groups vs combined VEH group at Wk12, with improvements seen from Wk4; highest efficacy was observed in the 7.5%-BID group (OG 7.5%-BID vs combined VEH: Wk4: IAL: -9.2 [-33.7%] vs -7.2 [-26.7%], P = .107; NIAL: -8.6 [-22.7%] vs -6.8 [-16.5%], P = .283; Wk12: IAL: -15.0 [-55.6%] vs -10.7 [-40.0%], P = .001; NIAL: -17.5 [-47.8%] vs -9.3 [-28.7%], P < .001). Clinically meaningful changes were observed in acne severity, with IGA response rate greater in all OG-treated groups than in combined VEH groups (OG 7.5%-BID vs combined VEH: Wk4: 4.1% vs 2.3%, P = .495; Wk12: 25.9% vs 9.8%, P = .004). Adverse events (AEs) occurred in 20.8%, 25.7% and 27.7% vs 19.2% and 26.0% of pts treated with OG 4%-QD, OG 7.5%-QD, and OG 7.5%-BID vs VEH-QD and VEH-BID, respectively. The most common AEs were nasopharyngitis, upper respiratory tract infection and application site pruritus.

Conclusions: OG-treated pts had reduced IAL and NIAL counts, and improved IGA scores, compared to VEH-treated pts from Wk4, with 7.5%-BID dosing producing the greatest response in all primary endpoints. OG gel was well tolerated at all tested doses during the 12-wk treatment period.

Commercial support: This study was funded by Dermira, Inc. All costs associated with development of this poster were funded by Dermira, Inc.

Volume

76

Issue

6 Suppl 1

First Page

AB184

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