Zyclara (imiquimod) Cream - 2 indications

Scroll down for more information on each indication:

• for the treatment of actinic keratoses; approved March 2010
• for the treatment of external genital and perianal warts; approved March of 2011

General Information

Zyclara contains the active ingredient imiquimod, which belongs to a class of drugs called immune response modifiers (IRM's). IRM's have shown both antitumor and antiviral activity in vivo. 

Zyclara is specifically indicated for the following:

• Zyclara Cream, 2.5% and 3.75% are indicated for the topical treatment of clinically typical, visible or palpable actinic keratoses (AK) of the full face or balding scalp in immunocompetent adults.
• Zyclara Cream, 3.75% is indicated for the topical treatment of external genital and perianal warts/condyloma acuminata (EGW) in patients 12 years or older.

Zyclara is supplied as a cream for topical administration as follows:

• Actinic Keratosis: Zyclara should be administered once daily to the skin of the affected area (either the entire face or balding scalp) for two 2-week treatment cycles separated by a 2-week no-treatment period
• External Genital Warts: Zyclara should be administered once daily to the external genital/perianal warts until total clearance or up to 8 weeks.

Mechanism of Action

Zyclara contains the active ingredient imiquimod, which belongs to a class of drugs called immune response modifiers (IRM's). IRM's have shown both antitumor and antiviral activity in vivo. The exact mechanism of action in which imiquimod activates the immune system is not yet known. However, it is known that imiquimod activates immune cells through the toll-like receptor 7, commonly involved in pathogen recognition, on the cell surface.

Side Effects

Adverse events associated with Zyclara Cream may include, but are not limited to, the following:

• local skin reactions
• erythema
• edema weeping/exudate
• flaking/scaling/dryness
• scabbing/crusting
• erosion/ulceration

Indication 1 - for the topical treatment of clinically typical, visible or palpable actinic keratoses (AK) of the full face or balding scalp in immunocompetent adults

Approved March of 2010

Clinical Trial Results

The FDA approval of Zyclara Cream was based on two double-blind, randomized, vehicle-controlled clinical studies. The studies enrolled 319 adults subjects with 5-20 typical visible or palpable AK lesions of the face or scalp. Zyclara Cream was applied to either the entire face (excluding ears) or balding scalp once daily for two 2-week treatment cycles separated by a 2-week no-treatment period. On a scheduled dosing day, up to two packets of the study cream were applied to the entire treatment area prior to normal sleeping hours and left on for approximately 8 hours. The subjects continued in the study for an 8- week follow-up period during which they returned for clinical observations and safety monitoring. Efficacy was assessed by AK lesion counts at the 8-week post-treatment visit. All AKs in the treatment area were counted, including baseline lesions as well as lesions which appeared during therapy. Complete clearance required absence of any lesions including those that appeared during therapy in the treatment area while partial clearance was defined as the percentage of subjects in whom the number of baseline AKs was reduced by 75% or more. The results are as follows:
Rates of Subject with Complete Clearance at 8 Weeks Post Treatment
Study One: Zyclara Cream: 25.9% vs. placebo: 2.5%. Study Two: Zyclara Cream: 45.6% vs. placebo: 10.1%.
Rate of Subjects with Partial Clearance (>75%) at 8 Weeks Post Treatment:
Study One: Zyclara Cream: 45.7% vs. placebo 18.8%. Study Two: Zyclara Cream: 73.4% vs. placebo: 26.6%.

Indication 2 - for the topical treatment of external genital and perianal warts/condyloma acuminata in patients 12 years or older

Approved March of 2011

Clinical Trial Results

In two double-blind, randomized, placebo-controlled clinical studies, 601 subjects with EGW were treated with 3.75% imiquimod cream, or a matching placebo cream. Studies enrolled subjects aged from 15 to 81 years. The baseline wart area ranged from 6 to 5579 mm (median 60 mm ) and the baseline wart count ranged from 2 to 48 warts. Most subjects had two or more treated anatomic areas at baseline. Anatomic areas included: inguinal, perineal, and perianal areas (both genders); the glans penis, penis 2 2 included: inguinal, perineal, and perianal areas (both genders); the glans penis, penis shaft, scrotum, and foreskin (in men); and the vulva (in women). Up to one packet of study cream was applied once daily. The study cream was applied to all warts prior to normal sleeping hours and left on for approximately 8 hours. Subjects continued applying the study cream for up to 8 weeks, stopping if they achieved complete clearance of all (baseline and new) warts in all anatomic areas. Subjects who achieved complete clearance of all warts at any time up to the Week 16 visit entered a 12-week follow-up period to assess recurrence. Complete clearance was defined as clearance of all warts (baseline and new) in all anatomic areas within 16 weeks from baseline. 

Study 1: Complete Clearance was reached by 27% versus 10% for Xyclara 3.75% versus placebo

Study 2: Complete Clearance was reached by 29% versus 9% for Xyclara 3.75% versus placebo