Olumacostat glasaretil (DRM01) for the treatment of acne vulgaris: Primary results from the DRM01-ACN02 phase 2b randomized controlled trial
Del Rosso J, Stein Gold L, Kircik L, Tan J, Maari C, Bissonnette R, Zib B, Quiring J, Webster G. Olumacostat glasaretil (DRM01) for the treatment of acne vulgaris: Primary results from the DRM01-ACN02 phase 2b randomized controlled trial. Journal of the American Academy of Dermatology 2017; 76(6 Suppl 1):AB184.
Journal of the American Academy of Dermatology
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.
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