A novel topical minocycline foam has been found to significantly reduce both inflammatory and noninflammatory lesions and improve acne scares in patients with moderate-to-severe acne vulgaris in phase three clinical trials.

American Academy of Dermatology guidelines recommends minocycline and doxycycline as first-line therapies for moderate and severe acne. However, concerns about side-effects limit their use.

No topical minocycline is currently licensed, but topical minocycline 4% foam has been tested in three phase three clinical trials and shown to produce significant improvements while minimizing systemic side effects associated with oral administration.

A total of 961 patients were enrolled in the first two identical randomized, double-blind phase three trials (466 in trial 04 and 495 in trial 05) and randomized 2: 1 to eleven-daily minocycline 4% foam or foam vehicle for 12 weeks.

In study 04, the mean reduction in inflammatory lesions was -14.13 with the minocycline 4% foam compared with -11.19 with foam vehicle (P = 0.0083), and in study 05, lesion count fell by -13.46 with minocycline foam compared with -10.70 with foam vehicle (P = 0.0051).

Significant reductions in non-inflammatory lesions were also seen with minocycline 4% foam in both studies (study 04: -16.45 vs -10.30 [P = 0.0042] and study 05: -13.20 vs -7.00 [P = 0.0320]).

One of the researchers Dr. Linda Stein Gold from the Henry Ford Health System, Detroit, said poor adherence to acne treatment is a problem. "Systemic acne therapy may have lower adherence rates than topical therapy, because of the lack of efficacy and the occurrence of side effects."

"The effectiveness of the active drug and the potentially lower risk of systemic side effects with the topical minocycline foam may improve treatment adherence," said Dr. Gold.  Surveys of patients have indicated that regarding topical treatments foams are generally preferred over creams, gels, and ointments. "The foam delivery system for topical drugs is easy to apply and does not leave to greasy or oily film on the skin after application," Dr. Stein Gold said.

The investigators pointed out that, although IGA-assessed treatment success did not reach statistical significance in study 04, there was a clear numerical advantage for minocycline 4% foam, and a significant advantage was seen when data from both studies were pooled.

The third phase 3 clinical trial

The failure to reach clinical significance in study 04 could have been due to the small number of patients enrolled so a third phase 3 clinical trial with 1507 patients has taken place to address this.

Topline results from this third phase three trial show the mean reduction in inflammatory lesion count at week 12 relative to baseline was -16.93 for the minocycline 4% foam treatment group and -13.40 for the vehicle treatment group (p<0.0001).

In addition,  30.80% of the active treatment group achieved IGA treatment success at week 12 compared with 19.63% for the vehicle treatment group (p<0.0001). There were no serious treatment-related adverse events and minocycline 4% foam appeared to be safe and well-tolerated. Foamix expects to make a drug application to the FDA by the end of the year for minocycline 4% foam (candidate drug FMX101) in moderate to severe acne.

Iain A Stuart, senior vice president of research and development at Foamix, said that the data from this third confirmatory phase three study for minocycline 4% foam are "impressive" and that the strong body of clinical data generated "suggest that it may be that patients an efficacious treatment in a convenient and safe topical foam formulation . "