Efficacy, Safety, and Tolerability of Oral DFD-29, a Low-Dose Formulation of Minocycline, in Rosacea: Two Phase 3 Randomized Clinical Trials.

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.