Sinecatechins Ointment, 15%: A Novel Treatment Option for External Genital and Perianal Warts

Program Chairperson, Past-President, American Society, for Colposcopy and Cervical Pathology, (ASCCP), Director, Women’s Clinic Student Health Center (Retired), University of California, Santa Barbara, Santa Barbara, CA

Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alabama at Birmingham, Senior Scientist, UAB Comprehensive Cancer Center, Birmingham, AL

Professor, Family Medicine, Professor, Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA

Obstetrician and Gynecologist, Private Practice, Department of Obstetrics and Gynecology, Northside Hospital, Atlanta, GA

Clinical Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, CA

DISCLOSURES
J. Thomas Cox, MD, is a consultant to Gen-Probe and Roche and is a member of the Speakers Bureau for GlaxoSmithKline, PharmaDerm, Graceway Pharmaceuticals, and BD Diagnostics. He has received financial/ material support from Merck, HPV Vaccine Data and Safety Monitoring Board.

Warner Huh, MD, has received grant/research support from Merck, GlaxoSmithKline, and Roche. He is a consultant for Roche, Helix, BioPharma, Qiagen, Hologic, and Inovio.

E. J. Mayeaux, Jr, MD, is a consultant and serves on the Speakers Bureau for PharmaDerm and Merck.

Michael Randell, MD, is a consultant and serves on the Speakers Bureau for Alaven Pharmaceuticals, Cord Blood Registry, Intuitive Surgical, Merck, Myriad Genetics, OmniGuide, PharmaDerm, Qiagen, Quest Diagnostics, SurgiQuest, Teva Pharmaceuticals, Vermillion, and Watson Pharmaceuticals.

Maida Taylor, MD, is a consultant for Everett Labs, Semprae Labs, ChemoSpain, PharmaDerm, Depomed, and Boehringer Ingelheim. This roundtable meeting and supplement were supported by PharmaDerm, A Division of Nycomed US Inc.

This roundtable meeting and supplement were supported by PharmaDerm, A Division of Nycomed US Inc.

ACKNOWLEDGMENTS

The authors wish to thank Mary Tom, PharmD, and Malik Cobb, PA-C, for their medical writing and editorial assistance.

INTRODUCTION

The panel discussed sinecatechins ointment, 15% (Veregen^®, PharmaDerm, Melville, NY, USA) because it is the newest therapeutic option added to the Centers for Disease Control and Prevention (CDC) sexually transmitted disease (STD) treatment guidelines for treatment of genital warts. Veregen is a topical ointment indicated for the treatment of external genital and perianal warts ([EGW] Condylomata acuminata) in immunocompetent patients 18 years of age or older.¹ It contains a proprietary, quantified mixture of catechins (85% to 95% by weight) and other components derived from green tea leaves (Camellia sinensis [L.] O. Kuntze). The main catechin in sinecatechins ointment, 15% is epigallocatechin gallate (EGCg), which comprises more than 55% of the total catechin content.¹

Catechins are an interesting group of compounds, which have been evaluated for a wide variety of potential health benefits.^2-4 Most notably, they have demonstrated antioxidant,^2,3 antiviral,^2,3 and immune-stimulatory activity.² The mechanism of action of sinecatechins ointment in the clearance of EGW is currently unknown. In vitro, sinecatechins had antioxidative activity, though the clinical significance of this finding is unknown.¹

PHARMACOKINETICS

Topically applied sinecatechins ointment is not systemically absorbed to a clinically relevant extent. Data obtained from pharmacokinetic studies show that there is minimal systemic uptake, with only 1 catechin detected; EGCg was detected in the serum in a very small number of subjects after local application of the ointment.⁵

EFFICACY

Data from 2 phase III randomized, double-blind, vehicle-controlled clinical studies support the efficacy and safety of sinecatechins ointment, 15%.^6-8 Both studies enrolled patients 18 years of age or older with EGW. A total of 502 patients were randomized to therapy with sinecatechins ointment, 15%, sinecatechins ointment, 10%, or vehicle in Study 1⁷ and 503 patients were randomized to 1 of these 3 treatments in Study 2.⁸ Overall, 397 received sinecatechins ointment, 15% and 207 received vehicle in the combined studies.⁶ Baseline demographic and clinical characteristics were similar in the treatment groups (Table 1).⁶ Nearly half the patients randomized to sinecatechins ointment, 15% or vehicle were women (46.5%), and the mean ± SD age in both treatment groups was 31 ± 12 years. Mean ± SD baseline wart number and area were also similar in both groups (8.4 ± 6.2 vs 7.6 ± 5.0, respectively, and 98.9 ± 138.0 mm² vs 90.9 ± 97.9 mm², respectively). In both groups, ointment was applied 3 times daily for up to 16 weeks or until complete clearance of all warts (baseline and new warts).

Demographic and baseline clinical characteristics of patients with EGW in sinecatechins ointment, 15% clinical trials⁶

Pooled data analysis demonstrated that sinecatechins ointment, 15% resulted in complete clearance of baseline and newly emerging warts in 53.6% of patients (P<.001 vs vehicle), including 60.4% of women (P=.010 vs vehicle) and 47.3% of men (P=.001 vs vehicle) (Figure 1).^1,9 The lower clearance rate observed in men compared with women, also seen in studies on other topical treatments for EGW, is likely attributed to the greater skin keratinization of the penile shaft , the most common site of EGW in men, which probably affects drug penetration.^7,8 It is noteworthy that these studies on sinecatechins ointment, 15% used a stringent/rigorous endpoint for EGW (clearance of all warts [baseline and new] vs clearance of baseline warts only). It is also important to recognize that there was a relatively high rate of complete clearance demonstrated in the vehicle group, possibly due to spontaneous disease regression.

Pooled data also demonstrated a shorter time to complete clearance with sinecatechins ointment, 15% than with vehicle treatment (Figure 2).⁹ Statistically significant differences between active and vehicle treatment groups were evident as early as Week 6 and maintained for the remainder of the treatment period. Timely wart clearance is most certainly desirable for the patient, and also may limit the duration of therapy and number of office visits.

Finally, recurrence rates 12 weeks post-treatment were low in the sinecatechins ointment, 15% group. Only 6.8% of the patients who achieved complete clearance in the sinecatechins-treated group experienced recurrence 12 weeks post-treatment (Figure 3).⁶

SAFETY

Sinecatechins ointment, 15% was well tolerated in these studies.⁶ Local and regional adverse reactions are summarized in Table 2.¹ Overall, the incidence of adverse events was similar across treatment groups. Treatment with sinecatechins ointment, 15% was, however, associated with a higher incidence of any local skin reaction than those receiving the vehicle only, as would be expected (85.9% vs 60.4%, respectively).⁶ The incidence of these events peaked early during therapy and subsided during the treatment course.⁵ In order to promote patient compliance, patients should be made aware of the potential for sinecatechins ointment, 15% to induce local reactions. The most common adverse reactions were local skin and application site reactions. During clinical trials, only 2.3% of subjects discontinued therapy due to adverse events, and only 2.6% required treatment interruption or dose reduction for any period of time due to irritation.⁹

Local and regional adverse events in sinecatechins ointment, 15% phase III clinical trials¹

DOSAGE AND ADMINISTRATION

Sinecatechins ointment, 15% is to be applied 3 times daily to all EGW until complete clearance of all warts or for a period of up to 16 weeks.¹ Patients should be instructed to wash their hands before and after application. They should also be informed that it is not necessary to wash of the ointment from the treated area prior to the next application. Counseling should further include discussion of the potential for the ointment to weaken condoms and vaginal diaphragms.

SUMMARY

Sinecatechins ointment, 15% is an effective and generally well-tolerated patient-applied botanical alternative for EGW treatment. The studies reviewed herein demonstrate that, relative to vehicle, sinecatechins ointment, 15% induces high rates of complete clearance, statistically significant early onset of action, and low rates of recurrence. We conclude that sinecatechins ointment, 15% is an effective first-line therapy for EGW.

The roundtable meeting and this supplement were supported by PharmaDerm, A Division of Nycomed US Inc.

Veregen^® (sinecatechins) Ointment, 15% is a topical ointment indicated for the treatment of external genital and perianal warts (Condylomata acuminata) in immunocompetent patients 18 years of age or older.

SAFETY INFORMATION

VEREGEN^® has not been evaluated to treat urethral, intra-vaginal, cervical, rectal, or intra-anal human papilloma viral disease and should not be used to treat these conditions. Avoid use of VEREGEN^® on open wounds.

Avoid exposure of VEREGEN^®-treated areas to sun/UV-light because VEREGEN^® has not been tested under these circumstances. Safety and efficacy of VEREGEN^® have not been established in immunosuppressed patients or patients under 18 years of age, or for the treatment of external genital and perianal warts beyond 16 weeks or for multiple treatment courses.

The most common adverse reactions are local skin and application site reactions including (incidence ≥ 20%) erythema, pruritus, burning, pain/discomfort, erosion/ulceration, edema, induration, and vesicular rash.

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