Efficacy, Safety, and Tolerability of Oral DFD-29, a Low-Dose Formulation of Minocycline, in Rosacea
Neal Bhatia, J.Q. Del Rosso, Linda Stein Gold, Edward Lain, Zoe Diana Draelos, Srinivas Sidgiddi, MVOR-1 and MVOR-2 Study Investigators, Kenneth Dawes, Sunil Dhawan, Rosalyn Elizabeth George, Cheryl Hull, Robert S. Haber, Jeffrey Adelglass, Javier Alonso‐Llamazares, Mark Amster, Francisco L. Badar, Sureka Bollepalli, Steven A. Davis, Oscar del Valle, J.Q. Del Rosso, Zoe Diana Draelos, David Fivenson, David L. Fried, Terry M. Jones, Steven Kempers, Francisco A. Kerdel, Michael H. Gold, Pinkas E. Lebovits, Neal Bhatia, Mark S. Lee, Mark A. McCune, Steven Grekin, Walter K. Nahm, Jorge Santander, Stephen M. Schleicher, Javier F. Chang, Linda Stein Gold, Matthew L. Miller, Leonardo M. Allende, Eddie Armas, Megan Couvillion, Jess J. DeMaria, Francisco Flores, Theresa Greene Knoepp, Edward Lain, Megan Brinkworth Vissing, Douglas Logan, Cindy E. Owen, Melody Lynn Stone, Janet DuBois, Diane E. Vargas, Hector Wiltz, Paul S. Yamauchi, Scott Guenthner, Cheryl Burgess, Thomas Dirschka, Athanasios Tsianakas, Johannes Niesmann, Jens Rossbacher, Sebastian Zimmer, S. Ekanayake‐Bohlig, R. Dominicus, Oliver Weirich, Beate Schwarz, Tanja Fischer, H. Brüning, Beatrice Gerlach, Udo Amann
Abstract
Introduction: A low-dose modified formulation of minocycline hydrochloride, DFD-29, is under evaluation for treating papulopustular rosacea (PPR). Objective: To determine the efficacy and safety of DFD-29, 40 mg, compared with doxycycline, 40 mg, and placebo for treating PPR. Design, Setting, and Participants: This study included data from 2 double-blind, placebo-controlled, phase 3 randomized clinical trials (MVOR-1 and MVOR-2) conducted between March 2022 and May 2023 at 61 centers in the US and Germany. Healthy adults 18 years and older with moderate to severe PPR were included. Interventions: Participants were randomized 3:3:2 to oral DFD-29 (minocycline hydrochloride capsules), 40 mg; doxycycline, 40 mg; or placebo once daily for 16 weeks. Main Outcomes and Measures: The coprimary efficacy outcomes were (1) proportion of participants with Investigator's Global Assessment (IGA) treatment success with DFD-29 vs placebo and (2) total inflammatory lesion count reductions with DFD-29 vs placebo. Secondary outcomes included comparisons between DFD-29 and doxycycline in coprimary outcomes and between DFD-29 and placebo in erythema reduction. Results: Of 653 participants enrolled, 323 were randomized in MVOR-1 (247 [76.5%] women; mean [SD] age, 47.2 [13.7] years) and 330 were randomized in MVOR-2 (249 [75.5%] women; mean [SD] age, 51.6 [14.0] years). DFD-29 demonstrated superior efficacy in IGA success rates compared with placebo (MVOR-1: treatment difference [TD], 32.9%; 95% CI, 19.6-46.2; P < .001; MVOR-2: TD, 34.1%; 95% CI, 21.3-46.8; P < .001) and compared with doxycycline (MVOR-1: TD, 18.0%; 95% CI, 5.0-31.1; P = .01; MVOR-2: TD, 28.3%; 95% CI, 17.4-39.3; P < .001). DFD-29 also showed superior efficacy in least-squares mean reductions in total inflammatory lesions vs placebo (MVOR-1: TD, -9.2; 95% CI, -11.5 to -6.9; P < .001; MVOR-2: TD, -6.8; 95% CI, -8.9 to -4.8; P < .001) and doxycycline (MVOR-1: TD, -4.7; 95% CI, -6.7 to -2.8; P < .001; MVOR-2: TD, -3.5; 95% CI, -5.4 to -1.6; P < .001). Adverse events with DFD-29, doxycycline, and placebo were reported in 32 of 121 (26.4%), 25 of 116 (21.6%), and 27 of 76 (35.5%), respectively, in MVOR-1 and 51 of 122 (41.8%), 40 of 121 (33.1%), and 30 of 82 (36.6%), respectively, in MVOR-2. The most common adverse events with DFD-29, doxycycline, and placebo were nasopharyngitis, reported in 4 of 121 (3.3%), 2 of 116 (1.7%), and 3 of 76 (3.9%), respectively, in MVOR-1 and 13 of 122 (10.7%), 10 of 121 (8.3%), and 13 of 82 (15.9%), respectively, in MVOR-2, and COVID-19, reported in 4 of 121 (3.3%), 3 of 116 (2.6%), and 4 of 76 (5.3%) in MVOR-1 and 7 of 122 (5.7%), 8 of 121 (6.6%), and 5 of 82 (6.1%) in MVOR-2. Conclusions and Relevance: In this study, DFD-29 was superior in efficacy to both doxycycline and placebo and demonstrated a favorable risk-benefit profile in the treatment of PPR. Trial Registration: ClinicalTrials.gov Identifiers: NCT05296629 and NCT05343455.