Efficacy of Oral DFD-29, a Low-Dose Minocycline Formulation, in Patients in Germany and Patients in the US: An Analysis of Two Phase 3 Trials

Abstract

Background: A modified low-dose formulation of minocycline hydrochloride 40 mg (DFD-29; now approved as Emrosi^TM) for treating inflammatory lesions of rosacea in the US. This pooled analysis of two phase 3 trials compared the efficacy of DFD-29 in patients in Germany and the US.

Methods: Two double-blind, placebo-controlled, phase 3 clinical trials among adults aged ≥18 years with moderate-to-severe rosacea were conducted in the US and Germany. Participants were randomized in a 3:3:2 ratio to oral DFD-29 (minocycline hydrochloride capsules) 40 mg, doxycycline 40 mg, or placebo once daily for 16 weeks. Key efficacy endpoints included the proportion of participants demonstrating Investigator’s Global Assessment (IGA) treatment success and reductions in total inflammatory lesion counts in the DFD-29 group compared to the placebo and doxycycline groups. Pooled sub-group analyses were conducted comparing efficacy in participants enrolled in the US and in Germany.

Results: Of the 653 participants enrolled (US, 557; Germany; 96), 245 were randomized to DFD-29 (US, 210; Germany, 35), 246 to doxycycline (US, 210; Germany, 36), and 162 to placebo (US, 137; Germany, 25). A significantly greater proportion of patients achieved IGA treatment success with DFD-29 vs placebo in both regions (US, 62.5% vs 29.2%; P<0.001; Germany, 63.3% vs 23.0%, P<0.001) and with DFD-29 vs doxycycline in the US (62.5% vs 39.3%; P<0.001). In Germany, a greater proportion of participants on DFD-29 achieved IGA treatment success vs doxycycline (63.3% vs 37.4%), although the difference did not reach statistical significance (P=0.064). DFD-29 also showed significantly superior efficacy in least-squares mean (LSM) reductions [SD] in total inflammatory lesions vs placebo and doxycycline, respectively, in both the US (-19.0 [0.56] vs -12.3 [0.72] and -14.8 [0.57], P<0.001 for both comparisons) and Germany (-19.3 [1.52] vs -7.0 [1.88] and -14.4 [1.53]; P<0.05 for both comparisons). DFD-29 was generally well tolerated, with no notable differences in the frequency or severity of reported adverse events between groups.

Conclusion: DFD-29 showed superior efficacy to both placebo and doxycycline 40 mg in treating the inflammatory lesions of rosacea. There were no clinically meaningful differences in DFD-29 efficacy versus placebo and doxycycline between geographic regions.