combination gel yielded superior ADA release into the skin. Moreover, the BPO 2.5%/ADA 0.3% gel was not found to be bioequivalent to different regimens of monad formulations.60
In the pivotal phase 3 study, efficacy and safety of BPO 2.5%/ADA 0.3% gel were compared with that of vehicle gel in patients with moderate to severe acne. A subpopulation of severe patients was also evaluated. The safety and tolerability of BPO 2.5%/ADA 0.3% was compared with BPO 2.5%/ADA 0.1%. The study was not designed or powered to compare efficacy of the 0.3% vs 0.1% formulations. A total of 503 patients were enrolled in the multicenter, randomized, double-blinded, parallel-group, vehicle- and active-controlled study. Subjects were randomized 3:3:1 to receive 0.3% drug, 0.1% drug, or vehicle gel. At baseline, patients were required to have an acne severity of moderate or severe (Investigator’s Global Assessment (IGA) = 3 or 4). The study medication was applied once daily for 12 weeks.61
BPO 2.5%/ADA 0.3% gel reached its co-primary efficacy endpoints. Treatment success rate was defined as at least a 2-grade improvement on IGA at week 12 compared with baseline. 33.5% of patients on the 0.03% drug were considered a treatment success, compared with 11.5% in the vehicle arm (P=.001). In addition, there was a 66.4% reduction in inflammatory lesions at week 12 (with a baseline mean lesion count of 39.2 lesions) in the active treatment arm. A greater degree of efficacy was observed in the severe acne subpopulation. 31.3% of patients achieved treatment success at week 12 vs 13.3% in the vehicle arm (P=.029), and there was a 71.8% reduction in inflammatory lesions vs 28.6% in the vehicle arm (P<.001).61
The drug was well tolerated, albeit with slightly more cutaneous AEs than reported in the BPO 2.5%/ADA 0.1% gel arm. There were a total of 15 AEs in the 0.3% drug group vs 2 AEs (both occurring in the same patient) in the 0.1% drug group. No AEs were reported in subjects on the vehicle. One subject in the 0.3% gel group discontinued from the study because of an AE (a flare of atopic dermatitis). There were no serious AEs during the study. Overall the mean tolerability scores in the 0.3% gel arm were less than mild, on a 4 point scale where 0 = none and 3 = severe.61
On the Horizon
While we currently have 2 new formulations of previously existing molecules, there are also several new chemical entities in development for the treatment of acne. In addition, new concentrations and novel delivery systems for some of our current medications will further add to the armamentarium of drugs available to treat acne. In the next few years there will be several new and different options available for use.
Topical Dapsone
Clinical trials for a new concentration of dapsone topical gel have been completed. This formulation is designed for once daily application.62 Further details on the efficacy and safety of the drug are not publicly available.
Clinical trials for a new concentration of dapsone topical gel have been completed. This formulation is designed for once daily application.62 Further details on the efficacy and safety of the drug are not publicly available.
DRM01
DRM01 is a new chemical entity in development for the treatment of acne. It is an inhibitor of coenzyme-A carboxylase, the enzyme responsible for the first and rate-limiting step in the production of fatty acids. In vitro, it has demonstrated a dose-dependent inhibition of lipid synthesis, and shown to decrease sebaceous gland size in an animal model.63
DRM01 is a new chemical entity in development for the treatment of acne. It is an inhibitor of coenzyme-A carboxylase, the enzyme responsible for the first and rate-limiting step in the production of fatty acids. In vitro, it has demonstrated a dose-dependent inhibition of lipid synthesis, and shown to decrease sebaceous gland size in an animal model.63
A phase 2a, first-in-human study has been completed evaluating safety, tolerability, and preliminary efficacy of the drug compared with vehicle. Patients with moderate to severe acne were enrolled in the study and randomized 1:1 to apply active drug or vehicle twice daily for 12 weeks. Patients were then followed post-therapy through week 16. Numerical improvements were noted at week 4, and statistical significance was achieved for all efficacy endpoints at week 12. A significantly greater mean reduction in both inflammatory (64% vs 46%; P=.0006) and comedonal (48% vs 29%; P=.0025) lesion counts were observed in the active drug compared with vehicle. Moreover, a statistically greater number of patients (almost 25%) in the active arm achieved a treatment success (>2 grade improvement in the IGA score) at week 12 compared with vehicle (P=.0070). The drug was well-tolerated and similar between the DRM01 and vehicle groups. Most local skin reactions were none to mild. Five subjects in the DRM01 group experienced a severe local skin reaction, which included severe erythema (1 subject) and severe burning/stinging (4 subjects).64
FMX101
Minocycline is commonly prescribed as an oral therapy for the treatment of AV and soft tissue infections. Because of stability issues, challenges have previously arisen in attempts to formulate it as a topical preparation. FMX101 is a topical minocycline foam currently in development for the treatment of acne. A phase 2, multicenter, randomized, double-blind trial has been completed at 3 study centers in Israel. One hundred and fifty patients with moderate to severe acne were enrolled and treated with once-daily application of either a 1% or 4% minocycline foam or vehicle. By week 12, a 72% (P<.001) and 73% (P<.05) reduction in inflammatory and comedonal lesions, respectively, were observed in the FMX101 4% group, which was statistically superior to vehicle. Moreover, 53% of patients using FMX101 4% were clear or almost clear vs 19.6% in the vehicle arm (P<.05). In addition, 36.2% of patients on the 4% drug were clear or almost clear along with a greater than 2 grades improvement, compared with 15.2% on vehicle (P<.05). There were no reported treatment-related AEs.65
Minocycline is commonly prescribed as an oral therapy for the treatment of AV and soft tissue infections. Because of stability issues, challenges have previously arisen in attempts to formulate it as a topical preparation. FMX101 is a topical minocycline foam currently in development for the treatment of acne. A phase 2, multicenter, randomized, double-blind trial has been completed at 3 study centers in Israel. One hundred and fifty patients with moderate to severe acne were enrolled and treated with once-daily application of either a 1% or 4% minocycline foam or vehicle. By week 12, a 72% (P<.001) and 73% (P<.05) reduction in inflammatory and comedonal lesions, respectively, were observed in the FMX101 4% group, which was statistically superior to vehicle. Moreover, 53% of patients using FMX101 4% were clear or almost clear vs 19.6% in the vehicle arm (P<.05). In addition, 36.2% of patients on the 4% drug were clear or almost clear along with a greater than 2 grades improvement, compared with 15.2% on vehicle (P<.05). There were no reported treatment-related AEs.65
SB204
Nitric oxide is a naturally occurring molecule in the body that possesses both anti-microbial and anti-inflammatory
Nitric oxide is a naturally occurring molecule in the body that possesses both anti-microbial and anti-inflammatory
