New Imiquimod Formulation for Actinic Keratosis published in JAAD

Study Examining New Short-Course Imiquimod Formulation in Actinic Keratosis published in Journal of the American Academy of Dermatology

Imiquimod 3.75% Is Now Available In Pharmacies Across Canada

TORONTO, ON, March 8, 2010 – 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 a 2-week treatment cycle. The study demonstrates that both formulations were superior to placebo, and that imiquimod 3.75% on a daily 2-week treatment cycle is superior to imiquimod 2.5% in treating actinic keratosis (AK) on a large surface area - the face or balding scalp.[i] 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) if left untreated.[ii]

Health Canada has recently approved imiquimod cream 3.75% (Zyclara™) as a topical cream for the treatment of multiple AKs located on the face or balding scalp in adults. It is now available in pharmacies across Canada.

The Phase III clinical trial program evaluated the safety and efficacy of imiquimod in patients averaging between five to 20 AKs in an area greater than 25cm2 on either the face or balding scalp. 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 per cent as compared to only a quarter of patients treated with placebo. Complete clearance, defined as the number of patients with zero AKs after treatment, was 36 per cent with imiquimod 3.75% versus 6 per cent with placebo. Additionally, partial clearance, defined as at least 75 per cent or greater reduction in total AKs, was achieved in 59 per cent of patients treated with imiquimod 3.75% versus only 23 per cent with placebo.[iii] Results for imiquimod 2.5% administered on the same frequency included a total AK lesion reduction of 72 per cent, complete clearance of 31 per cent and partial clearance of 48 per cent respectively.[iv] The clinical trial program was led by Neil Swanson, M.D., professor and chairman, Department of Dermatology, Oregon Health and Science University

“The low concentration of imiquimod enhances tolerability, so patients can use it in a simple daily-dosing regimen,” said Dr. Charles Lynde, dermatologist and assistant clinical professor at the University of Toronto. “This helps increase compliance which ultimately helps achieve long term medical clearance of lesions and desired cosmetic outcomes.”

Approximately half, 40 to 60 per cent, of SCCs begin as untreated AKs.[v] Anyone who has previously had an AK is at a higher risk for developing new AKs.[vi] If AKs are visible on the surface of the skin, it is likely that there are more invisible AKs just below the skin’s surface, known as subclinical lesions.[vii] Therapies that treat surface areas greater than 25 cm2 may account for greater reductions in both AK lesions and subclinical lesions.[viii]

“With the low concentration imiquimod 3.75% you can treat a large surface area which includes lesions you can see and those that are under the skin’s surface, which means a greater chance of treating AK effectively,” says Dr. Lynde. “We know that patients prefer prescription creams over more invasive therapies, so the Health Canada approval offers another safe and effective option.”

Study Design In two double-blind, placebo-controlled studies, 479 adults 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. Patients were enrolled at 25 study centers in the United States.

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

Local skin reactions such as erythema are consistent with treatment response. The most commonly reported severe local skin reactions with the 2-week treatment cycle with a 3.75% and 2.5% concentration were, respectively, erythema (25%, 14%), scabbing/crusting (14%, 9%), erosion/ulceration (11%, 9%), and flaking/scaling/dryness (8%, 4%).[x] 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, color, size and texture. 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, detection and early treatment are important. About Graceway Pharmaceuticals Graceway Pharmaceuticals Canada ("Graceway Canada"), headquartered in London, ON, is a wholly owned subsidiary of Graceway Pharmaceuticals, LLC, based in Bristol, TN in the United States. Graceway 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 Canada include, among others, Aldara™ (imiquimod 5%) Cream, QVAR™ (beclomethasone dipropionate metered dose aerosol) and other products in women’s health and cardiology.

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For more information please contact: Environics Communications: Alison O’Mahony (416) 969-2745 or Daria Hopej (416) 969-2826 aomahony@environicspr.com; dhopej@environicspr.com

________________________________ [i] <#_ednref1> Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Results.

[ii] <#_ednref2> Skin Cancer Foundation. “Actinic Keratosis and Other Precancers.” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on: September 2, 2009. Page 1, 3rd Paragraph.

[iii] <#_ednref3> Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Results.

[iv] <#_ednref4> Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Results.

[v] <#_ednref5> Skin Cancer Foundation. “Actinic Keratosis and Other Precancers.” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on: September 2, 2009. Page 1. 3nd Paragraph.

[vi] <#_ednref6> Skin Cancer Foundation. “What is Actinic Keratosis” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on February 8, 2010. 8th Paragraph.

[vii] <#_ednref7> Skin Cancer Foundation. “What is Actinic Keratosis” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on February 8, 2010. 7th Paragraph.

[viii] <#_ednref8> Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Background.

[ix] <#_ednref9> Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Methods, Study design and study cream dosing.

[x] <#_ednref10> Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Methods, Safety evaluations.

[1] Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Results.

[1] Skin Cancer Foundation. “Actinic Keratosis and Other Precancers.” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on: September 2, 2009. Page 1, 3rd Paragraph.

[1] Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Results.

[1] Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Results.

[1] Skin Cancer Foundation. “Actinic Keratosis and Other Precancers.” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on: September 2, 2009. Page 1. 3nd Paragraph.

[1] Skin Cancer Foundation. “What is Actinic Keratosis” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on February 8, 2010. 8th Paragraph.

[1] Skin Cancer Foundation. “What is Actinic Keratosis” Available at: http://www.skincancer.org/actinic-keratosis-and-other-precancers.html. Accessed on February 8, 2010. 7th Paragraph.

[1] Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Background.

[1] Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Methods, Study design and study cream dosing.

[1] Swanson, N et al. (2010) “Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles”. Methods, Safety evaluations.

Posted: March 2010

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