Dermira’s novel topical sebum inhibitor -- DRMO1 -- may put the brakes on facial acne, according to topline results from a Phase 2b dose-ranging study that is paving the way toward a Phase 3 Clinical Program.

DRM01 is a novel, small molecule designed to inhibit sebum production following topical application.

In the study, DRM01 demonstrated statistically significant improvements in all primary endpoints compared to vehicle at the highest dose and in most primary endpoints at the two lower doses. In addition, DRM01 was well-tolerated with adverse events primarily mild or moderate in severity.

The initiation of the Phase 3 program is targeted for the first half of 2017, subject to an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA).

Study Details

In the Phase 2b study, the primary endpoints were absolute changes from baseline in inflammatory and non-inflammatory lesion counts and the proportion of patients achieving at least a two-point improvement from baseline on the five-point Investigator’s Global Assessment (IGA) scale. Each endpoint was measured at the end of a 12-week treatment period.

DRM01 demonstrated statistically significant improvements from baseline to week 12 relative to vehicle in all primary efficacy endpoints at the highest dose of DRM01 (7.5% twice daily), which also demonstrated the highest efficacy in all primary endpoints compared to the two lower doses. The number of inflammatory lesions in patients treated with this highest dose of DRM01 was reduced by an average of 15.0 compared to 10.7 in patients in the combined vehicle group (p=0.001), or an average percentage reduction of 55.6 percent compared to 40.0 percent (p<0.001). The number of non-inflammatory lesions in patients treated with this same dose of DRM01 was reduced by an average of 17.5 compared to 9.3 in patients in the combined vehicle group (p<0.001), or an average percentage reduction of 47.8 percent compared to 28.7 percent (p<0.001). At the end of the 12-week treatment period, 25.9 percent of patients treated with this highest dose of DRM01 achieved a successful improvement in the IGA score (minimum two-grade improvement) compared to 9.8 percent of patients in the combined vehicle group (p=0.004).

Overall, a dose response was observed for all three primary endpoints. At the 4.0% once daily dose, DRM01 demonstrated statistically significant improvements in all three primary endpoints compared to the combined vehicle group. At the 7.5% once daily dose, DRM01 demonstrated statistically significant improvements in the inflammatory and non-inflammatory lesion count endpoints compared to the combined vehicle group, and approached statistical significance in the IGA improvement endpoint (p=0.06).

Based on the results, Dermira believes each of the three doses evaluated in the Phase 2b study could be a viable dose for a Phase 3 program. Further data analysis and an end-of-Phase 2 meeting with the FDA are expected to determine the precise dose and design for the Phase 3 program.

Consistent with the Phase 2a study, DRM01 was well-tolerated. Adverse events were primarily mild or moderate in severity. The most frequently reported adverse events across all three DRM01 treatment groups were common cold (nasopharyngitis; 5.4 percent), upper respiratory tract infection (2.5 percent) and application site itching (pruritus; 2.5 percent). No treatment-related serious adverse events were reported.

“DRM01 is an investigational, topical agent that represents a novel approach to acne treatment by targeting sebum production, a key contributing factor in the development of acne,” says Linda Stein Gold, M.D., director of Dermatology Clinical Research and division head of Dermatology at Henry Ford Hospital in Detroit, Michigan and one of the investigators for the DRM01 Phase 2b trial, in a news release. “Based on these results, DRM01 could represent a potentially meaningful new treatment for the dermatology community that offers patients a safe, well-tolerated and effective alternative to current options.”

The DRM01 Phase 2b trial was a randomized, multi-center, double-blind, parallel-group, vehicle-controlled study designed to assess the safety and efficacy of DRM01 compared to vehicle in adult patients 18 and older with moderate-to-severe facial acne vulgaris. A total of 420 patients were enrolled in the study at 34 sites in the United States and Canada. Inclusion criteria required a minimum of 20 inflammatory lesions and 20 non-inflammatory lesions and an IGA score of three or greater on a five-point scale that ranges from a score of zero, representing clear skin, to a score of four, representing severe disease. Patients were randomized into five separate arms and instructed to apply DRM01 at concentrations of 4.0% once daily (n=106), 7.5% once daily (n=110) or 7.5% twice daily (n=101), or to apply vehicle once or twice daily (n=53 and n=50, respectively), in all cases for 12 weeks. Consistent with the previous Phase 2a trial and in accordance with the published FDA draft guidance for the development of acne drugs, the primary endpoints were absolute changes from baseline in inflammatory and non-inflammatory lesion counts and the proportion of patients achieving at least a two-point improvement from baseline in the five-point IGA score. Each endpoint was measured at the end of the 12-week treatment period.