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FDA Accepts NDA for New Imiquimod Product

Data Demonstrate New Imiquimod Formulation as Short Course Treatment for Actinic Keratosis – FDA Accepts NDA for New Imiquimod Product –

BRISTOL, Tenn.--(BUSINESS WIRE) July 31, 2009--Results from a Phase III program evaluating short-course regimens of two concentrations of imiquimod cream (3.75% and 2.5%) demonstrated imiquimod 3.75%, administered daily on two two-week treatment cycles, separated by a two-week non-treatment period, produced clearance rates superior to placebo for actinic keratosis (AK). Imiquimod 3.75% was also more effective than 2.5% with comparable safety. The new data, presented today at the American Academy of Dermatology Summer Academy Meeting, are in a new drug application (NDA) accepted for review by the U.S. Food and Drug Administration for imiquimod 3.75% utilizing a two-week cycle regimen in the treatment of AK.

With respect to the treatment of AK, the existing approved 5% imiquimod formulation is indicated only for the treatment of nonhyperkeratotic, nonhypertrophic AK on a very limited area of the skin (i.e., less than 25 cm2) for a full 16 weeks of treatment. The intent of the clinical studies conducted with the new 3.75% imiquimod formulation was to evaluate a new treatment paradigm for clinically typical AK lesions on patients with extensive disease (i.e., patients with 5 to 20 AK lesions over the full face or balding scalp). “We believe that the new 3.75% imiquimod formulation and its two-week treatment cycle regimen could offer physicians a new predictable treatment option for their patients who present with typical AK lesions on affected fields of skin,” said Jefferson J. Gregory, Chairman and CEO of Graceway Pharmaceuticals.

Total AK lesions (baseline 5 to 29 on the face and/or scalp) were reduced with imiquimod by 82% (imiquimod 3.75%) and 72% (imiquimod 2.5%). The data revealed that patients treated with 3.75% cream and 2.5% cream imiquimod showed greater rates of complete clearance of AKs – 36% and 31%, respectively, compared to 6% for patients treated with placebo. Complete clearance required clearance of all lesions, both those evident at baseline as well as new lesions revealed during treatment. Imiquimod treatment also resulted in higher partial clearance rates, defined as ≥ 75 % reduction in AK count, in 59% (imiquimod 3.75%), and 48% (imiquimod 2.5%) of patients, versus only 23% of placebo treated patients.

The new data also showed that sub-clinical AK lesions (lesions that were present, but not clinically apparent at baseline) become apparent in the field of treatment during treatment with the 3.75% formulation. In the study, more than 85% of subjects treated with 3.75% experienced an increase in AK lesions relative to the number present at baseline within the field of treatment. Reported clearance rates reflect treatment of both visible/palpable lesions and new lesions revealed during treatment.

“Topical imiquimod 5% can be difficult for some AK patients because of the required full 16-week dosing,” said Dr. Neil Swanson, professor and chairman, Department of Dermatology, Oregon Health and Science University. “These data demonstrate the two-week cycle regimen at a lower concentration may be an effective and convenient treatment option.”

About the Studies

In four double-blind, placebo controlled studies, 969 adults with 5 to 29 AK lesions in a treatment area >25 cm2 (full face or balding scalp) were randomized to either placebo, imiquimod 3.75% or 2.5% (1:1:1). Patients applied up to 500 mg of cream daily for two cycles, two-week or three-week, separated by a no-treatment interval of two or three weeks. Primary efficacy was assessed eight weeks after the last dose.

Data from the Phase III program revealed that both the 3.75% and 2.5% imiquimod formulations administered once-daily over a large surface area (>25 cm2) of the full face or balding scalp in two or three week cycles were statistically superior to placebo. The data revealed that 3.75% imiquimod patients had 36% complete clearance of AK versus 6% for placebo. The 2.5% imiquimod patients showed 31% complete clearance of AK versus 6% for placebo. The differences between the 3.75% and 2.5% concentrations were statistically significant for partial clearance and percentage reduction in lesion counts from baseline. Comparable efficacy was demonstrated for both regimens (two weeks and three weeks) at each concentration.

The majority of subjects in all imiquimod groups had increases in the number of lesions from baseline during treatment, consistent with the unmasking of subclinical AK lesions. Clearance rates reflect treatment of both visible/palpable and new lesions.

Local skin reactions such as erythema are consistent with treatment response. The most commonly reported severe local skin reactions with the 3.75% concentration during the two-week treatment cycle regimen were erythema (25%), scabbing/crusting (14%), ulceration (11%), and flaking /scaling/dryness (8%). The longer three-week cycle regimen was associated with a higher frequency of adverse events, rest periods, and severe local skin reactions than was observed with the two-week cycle regimen.

“We are pleased with these data and will work closely with the FDA as they review our application for this new product,” said Mr. Gregory. “This development program and application represent our strong commitment to delivering advanced topical treatments that can provide doctors with more effective options for their patients.”

About AK

AKs are dry, scaly, rough-textured patches or lesions that form on the outermost layer of the skin after years of exposure to ultraviolet (UV) light, such as sunlight. These lesions typically range in color, from skin-toned to reddish brown, and in size, from that of a pinhead to larger than a quarter.

AKs are considered the earliest stage in the development of skin cancer and have the potential to progress to squamous cell carcinoma, a type of skin cancer that can be fatal.


ALDARA is the brand name for imiquimod cream, 5%, which is an immune-response modifier. Aldara Cream is a skin-use only (topical) prescription medicine used to treat certain types of actinic keratosis on the face and scalp of adults with normal immune systems.

When using Aldara Cream, the most common side effects involve skin reactions in the application area. These include redness, swelling, erosions, weeping, scabbing, itching and burning. Most skin reactions are considered mild to moderate.

When using Aldara Cream for actinic keratosis, exposure to sunlight (including sunlamps) should be avoided or minimized during use of Aldara Cream because of concern of heightened sunburn susceptibility. Patients should be warned to wear protective clothing (e.g., hat) when using Aldara Cream.

About Graceway Pharmaceuticals, LLC

Graceway Pharmaceuticals, LLC ("Graceway"), headquartered in Bristol, TN, is a pharmaceutical company focused on acquiring, in-licensing, and developing branded prescription pharmaceutical products. Current prescription products marketed by Graceway include ALDARA® (imiquimod) Cream, 5%, Maxair®Autohaler® (pirbuterol acetate inhalation aerosol), Atopiclair® Nonsteroidal Cream, and Estrasorb® (estradiol topical emulsion). ALDARA®, Maxair®, Autohaler®, Atopiclair®, and Estrasorb® are trademarks owned by or licensed to Graceway. For more information on Graceway's products, including important safety information, please visit<>.


Swanson N, Rosen T, Berman B, et al. Optimizing Imiquimod for Treating Actinic Keratosis of the Full Face or Balding Scalp: Imiquimod 2.5% and 3.75% Applied Daily for two 2-week or 3-week cycles. Poster presented at: The 12th World Congress on Cancers of the Skin in Tel Aviv, Israel, May 3-5, 2009.

Contacts Graceway Pharmaceuticals, LLC James Lee, MD, Ph.D., Chief Medical Officer 800-328-0255


Glenn Silver Vice President Chamberlain Healthcare Public Relations an inVentiv health company 111 Broadway, 19th Floor New York, NY 10006 T 212-884-0646 F 212-884-0628 C 201-486-0952

Posted: August 2009