ST. LOUIS — An investigational ointment containing extract of green tea successfully clears genital warts in about 60% of patients, Karl Beutner, M.D., said at the annual meeting of the Society for Investigative Dermatology.
The ointment, polyphenon E, is being developed by MediGene AG, Martinsried, Germany. The active ingredient is 80% tea polyphenols. The main catechin in the extract is (−)-epigallocatechin gallate (EGCG), which has been shown to induce apoptosis in human carcinoma cell lines.
“It's a strong antioxidant that inhibits a number of different enzymes,” said Dr. Beutner, chief medical officer at Dow Pharmaceutical Sciences, Petaluma, Calif. “Unpublished reports indicate that it induces a pro-Th1 cytokine profile not dissimilar to that of imiquimod.”
The three-armed, placebo-controlled trial randomized 502 patients to an active ointment of 10% or 15% concentration, or the vehicle, which contains isopropyl myristate. Patients had an average of eight warts (2–30), covering an average area of 95 mm
Patients applied the ointment three times a day for up to 16 weeks, or until all warts cleared. Those who cleared completely were enrolled in a 12-week follow-up trial to assess recurrence rates.
“The primary end point was clearance of all warts—the baseline warts and any warts that developed during treatment,” Dr. Beutner said. “This is an important distinction because other trials report the response in terms of only clearing the baseline warts. This was a stringent end point. They had to be clear of all warts.”
At the end of the 16-week treatment period, about 59% of patients in both active groups had complete clearance of their baseline warts, compared with about 34% of vehicle patients. Complete clearance of all warts occurred in 56% of the 10% group, 57% of the 15% group, and almost 34% of the vehicle group. Average time to response was 11 weeks.
About 80% of those in both active groups had more than 50% clearance. Less than 10% in either active group failed to respond. Women responded better than men, with about 65% of women and 50% of men in both active groups achieving complete clearance. Ongoing investigation is looking at whether the ointment is more effective on the moist skin of the vulvar area than on the dry skin of the penis, Dr. Beutner said.
During the 12-week follow-up period, 8.8% of those in the vehicle group experienced recurrence of baseline warts, compared with 6.5% of the group receiving the 15% formulation and 8.3% of the group receiving the 10% formulation. No new warts appeared in the vehicle group, however, while new warts did appear in 8% of the group receiving the 10% formulation and in 3.7% of the group receiving the 15% formulation.
About 87% of the active patients and 72% of the vehicle patients experienced at least one adverse event; events peaked at 2 weeks and then declined throughout the trial. Most were mild to moderate and included erythema, erosion, excoriation/flaking, edema, and induration. Only 1% of the patients discontinued use because of an adverse event. About 20% of the vehicle patients also had a mild to moderate local reaction.
The only serious events related to the study drug were two cases of vulvovaginitis, judged to be application site reactions.
Clinical trials for the ointment have been completed for the genital warts indication, Dr. Beutner said. MediGene AG also is conducting a phase II trial of the ointment for the treatment of actinic keratosis. Dr. Beutner is a consultant for the company.