Reviewed: Gross G, Meyer K-G, Pres H, Thielert C, Tawfik H, Mescheder A. A randomized, double-blind, four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of two galenic formulations of Polyphenon® E in the treatment of external genital warts. J Eur Acad Dermatol Venereol. 2007;21:1404–1412.
Of all the sexually transmitted diseases (STDs), genital warts has had one of the highest increases in incidence rate in recent years. External genital warts are benign squamous cell tumors caused by human papilloma viruses (HPVs). It is estimated that 0.5-1.0% of the general population is infected with HPV. Few treatments, with varying degrees of efficacy, are available and those that are available are associated with adverse side effects such as itching, edema, ulcerations, burning, and pain. Furthermore, none of the available treatments eliminate the source of the disease; therefore, recurrence is common. Studies conducted in China have shown that polyphenols are efficacious in treating genital warts and are associated with minimal pain and inflammation. Polyphenon® E (Mitsui Norin Co., Ltd., Tokyo, Japan), an extract of catechins derived from the leaves of green tea (Camellia sinensis, Theaceae), has a high polyphenol content and has been shown to have antitumor and anti-inflammatory activities. The objective of this study was to evaluate the efficacy and safety of Polyphenon E in the treatment of external genital warts.
Men and women aged 18 years or older, with up to 30 external genital warts (total wart area: 12-600 mm2), were recruited into this randomized, double-blind, placebo-controlled study. This multicenter phase II/III study was conducted in 20 German and 8 Russian health facilities. Patients with a current outbreak of Herpes genitalis or similar infection were ineligible. The patients were randomly assigned to 1 of 4 treatments according to a 2:1 active: placebo ratio stratified by sex. The active treatments involved the use of Polyphenon E 10% cream and Polyphenon E 15% ointment. For the corresponding placebo treatments, Polyphenon E was replaced with higher amounts of all of the base ingredients in the cream and with white petroleum and white wax in the ointment.
Polyphenon E (anticipated dose: <250 mg per application) or placebo was applied topically to all external genital warts 3 times daily until complete clearance of all warts or for a maximum of 12 weeks. Patients were evaluated at baseline, every other week until 8 weeks, and at 12 weeks. The main outcome measures were total wart area (clearance rate) and adverse events. The intention-to-treat (ITT) population included 238 patients (122 men and 116 women), and the per-protocol (PP) population included 225 patients (115 men and 110 women).
A total of 221 patients completed the study. No significant differences in the complete clearance rate of warts were observed between the placebo cream and ointment groups (ITT and PP populations). After treatment with 15% Polyphenon E, complete clearance of baseline warts was observed in 59% of the patients (P = 0.0066 compared with placebo), and a 75-100% reduction in wart area was observed in 80.8% of the patients (P = 0.0001 compared with placebo) in both the ITT and PP populations. There was no significant sex effect: complete clearance was achieved in 61% of the men and in 56.8% of the women (P > 0.05). No significant differences in clearance rates were observed between the Polyphenon E 10% cream and placebo groups. Recurrence rates for the Polyphenon E 15% ointment, Polyphenon E 10% cream, and placebo were 10.6%, 11.8%, and 10.3%, respectively. Local skin reactions to Polyphenon E were mild-to-moderate, and only 7.9% of the patients were observed to have adverse reactions, none of which were serious.
The authors conclude that Polyphenon E 15% ointment “proved to be efficacious and safe” for the treatment of external genital warts in both sexes. Because of these findings, the Polyphenon E 15% ointment will be evaluated further in prospective clinical studies.
A formulation using the green tea extract studied in this trial was approved by the US Food and Drug Administration (FDA) in 2006 as a prescription drug for the external treatment of genital warts caused by the human papilloma virus.1 This is the first chemically-complex “botanical drug” approved by the FDA in about 50 years. The drug, known as VeregenTM, is produced by Medigene AG of Martinsried, Germany, and it is to be marketed in the United States by Bradley Pharmaceuticals of Fairfield, New Jersey.
—Brenda Milot, ELS
1. Blumenthal M. FDA approves special green tea extract as a new topical drug for genital warts. HerbalGram. 2007;74:62-63.