Graceway Announces Journal of the American Academy of Dermatology Publishes Articles on New Short-Course Imiquimod Formulation in Actinic Keratosis

Data Suggest Short-Course Imiquimod 3.75% Produced Statistically Significant Outcomes

The Journal of the American Academy of Dermatology (JAAD) has published Phase III data evaluating the safety and efficacy of imiquimod cream at two doses – 2.5% and 3.75% – administered daily on either 2-week or 3-week treatment cycles. While all study arms met the primary endpoint of complete clearance versus placebo, data suggest that, of the regimens studied, imiquimod 3.75% on a 2-week cycle is superior in treating actinic keratosis (AK) on a large surface area – the full face or balding scalp. AKs are considered to be the earliest stage in the development of skin cancer and have the potential to progress to squamous cell carcinoma (SCC).

The Phase III clinical trial program evaluated the safety and efficacy of imiquimod in patients averaging between five to 20 AKs at baseline. Imiquimod cream 3.75% administered once daily for two 2-week treatment cycles, separated by a 2-week non-treatment period, reduced total AK lesions by 82 percent as compared to a 25 percent lesion reduction in patients treated with placebo. Complete clearance, defined as the number of patients with zero AKs after treatment, was 36 percent with imiquimod 3.75% versus 6 percent with placebo. Additionally, partial clearance, defined as at least 75 percent or greater reduction in total AKs, was achieved in 59 percent of patients treated with imiquimod 3.75% versus only 23 percent with placebo.

“These studies evaluated convenient dosing of imiquimod over a short duration of treatment,” said Neil Swanson, M.D., lead investigator of the 2-week study and Professor and Chairman, Department of Dermatology, Oregon Health and Science University. “The lower concentrations of imiquimod allowed patients to use it daily on large areas of the skin over the face or balding scalp, ultimately treating more AKs – both lesions present at baseline, as well as lesions revealed during treatment. This may change the way physicians treat AK.”

Study Results
Results of the 2-week treatment cycle of imiquimod 3.75% and 2.5% found:

Total AK lesions were reduced by 82% (imiquimod 3.75%) and 72% (imiquimod 2.5%), versus 25% with placebo.
Imiquimod 3.75% and 2.5% showed complete clearance of AKs at 36% and 31%, respectively, versus 6% with placebo.
Partial clearance rates were 59% (imiquimod 3.75%) and 48% (imiquimod 2.5%), versus 23% with placebo.
Local skin reactions such as erythema were consistent with treatment response. The most commonly reported severe local skin reactions with the 3.75% and 2.5% concentrations were erythema (25% vs. 14%), scabbing/crusting (14% vs. 9%), erosion/ulceration (11% vs. 9%) and flaking/scaling/dryness (8% vs. 4%), respectively.
“We are encouraged by these data and have submitted results from the 3.75% dose utilizing the 2-week cycle to the FDA as part of an NDA, in an effort to continue providing effective treatments for patients with AK,” said James Lee, M.D., Ph.D., Chief Medical Officer, Graceway Pharmaceuticals, LLC.

Results of the 3-week treatment cycle of imiquimod 3.75% and 2.5% found:

Total AK lesions were reduced by 80% (imiquimod 3.75%) and 67% (imiquimod 2.5%), versus 24% with placebo.
Imiquimod 3.75% and 2.5% showed complete clearance of 34% and 25%, respectively, versus 6% with placebo.
Partial clearance rates were 54% (imiquimod 3.75%) and 43% (imiquimod 2.5%), versus 13% with placebo.
The longer 3-week cycle regimen was associated with a higher frequency of adverse events, rest periods, and severe local skin reactions than was observed with the 2-week cycle regimen. The most commonly reported severe local skin reactions with the 3.75% and 2.5% concentrations were erythema (45% vs. 28%), scabbing/crusting (35% vs. 23%), erosion/ulceration (30% vs. 24%), scabbing/crusting (35% vs. 23%), flaking/scaling/dryness (13% vs. 11%) and edema (13% vs. 7%), respectively.
“Surprisingly, efficacy did not appear to increase using 3-week cycles as compared with using 2-week cycles,” said C. William Hanke, M.D., lead investigator of the 3-week study and Visiting Professor, Dermatology, University of Iowa-Carver College of Medicine. “Further studies will evaluate imiquimod for sustained clearance of AKs, beyond the 8-week follow-up assessed in these studies.”

Study Design
In four Phase III double-blind, placebo-controlled studies, 969 adults (775 male and 194 female) with five to 20 AK lesions in a large treatment area (full face or balding scalp) were randomized to placebo, imiquimod 3.75% or imiquimod 2.5% (1:1:1). Patient characteristics by age, sex, race, ethnicity, skin type, treatment location and baseline lesions were comparable across groups. In the 2-week and 3-week studies, patients were enrolled at 25 and 26 study centers, respectively, in the United States in two identically-designed studies conducted in parallel.

Patients applied up to two packets (250 mg each) daily for two cycles, 2-week or 3-week, separated by a no-treatment interval of two or three weeks, respectively. Primary efficacy was assessed eight weeks after the last dose.

About Actinic Keratosis
AK is a sign of sun damage resulting from long-term exposure to harmful UV rays. The sun’s rays cause changes in the size, shape, and organization of the top layer of skin cells, also known as the epidermis, and just below it. These cellular mutations can then form AKs.

AK is considered a pre-cancer and may often be confused with age spots, eczema or psoriasis. AKs are small, red, sometimes scaly or rough patches that can be found on skin most often exposed to the sun like the face, bald scalp, hands, shoulders and arms. AKs can vary in shape and color, ranging from red to light or dark tan, pink, or a combination of these. These lesions may range from the size of a pinhead to larger than a quarter and may feel dry and rough like sandpaper. In the beginning, AKs can be so small that they are often identified by their rough texture rather than by sight.

Some AKs will develop into a serious form of skin cancer called squamous cell carcinoma, or SCC. If left unchecked, this cancer can spread to other areas of the body and organs. Because it is difficult to predict whether an AK will develop into cancer, it is important to discuss any changes in your skin with a doctor.

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. Graceway initially acquired the imiquimod franchise as part of its acquisition of 3M’s (NYSE: MMM) branded pharmaceutical business in the United States, Puerto Rico, Canada and Latin America. Graceway has also recently completed acquisitions of other molecules or compounds from, among other companies, Pfizer, Inc. (NYSE: PFE) and Gilead Sciences, Inc. (NASDAQ: GILD). 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

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