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Four New Studies Presented at the World Congress of Dermatology Show Potential in Treating Precancerous Skin Disease, Actinic Keratosis

~ By 2031, projected non-melanoma skin cancer cases to increase by 93 per cent from 2004 - actinic keratosis a precursor ~

Please Note: This information is intended for Canadian media only.

THORNHILL, ON, June 7, 2011 /CNW/ - LEO Pharma Inc. has announced the results of clinical data from four phase III studies of ingenol mebutate gel, an investigational treatment for actinic keratosis (AK). AK - caused by long-term UV exposure - is a precancerous skin condition, which can lead to squamous cell carcinoma (SCC), a non-melanoma form of skin cancer.1 SCC is the second most common form of skin cancer and is an increasingly important health issue worldwide.2

The study results - presented for the first time at the 22nd World Congress of Dermatology - evaluated the efficacy and safety of ingenol mebutate (0.05%) applied once-daily for two consecutive days to actinic keratoses (multiple lesions) on the body. The other two studies evaluated the efficacy and safety of ingenol mebutate (0.015%) applied once-daily for three consecutive days to actinic keratoses on the face and scalp. The primary endpoint for all four studies was complete clearance rate of actinic keratosis lesions at the day-57 visit, an endpoint that was met with statistical significance in each study.

"Despite its increasing prevalence in Canada and around the globe, there is very little awareness about actinic keratosis among the general population," says Christine Jackson, Executive Director, Canadian Skin Patient Alliance. "There is much talk about skin cancer, but not enough attention is given to AK as a beginning warning sign, even when studies show many cases of skin cancer begin as actinic keratosis."

NON-MELANOMA SKIN CANCER ON THE RISE IN CANADA

The incidence for non-melanoma skin cancer in Canada are projected to move dramatically upwards over the next decades due to a growing and aging population - from an estimated annual average of 75,953 between 2000 and 2004 to 147,000 in 2031 (an increase of 93 per cent) - representing a large burden of treatment costs and lost productivity.3 This makes primary prevention of actinic keratosis through sun avoidance and sunscreens all the more crucial. Once damage has occurred, the focus turns to secondary prevention through early detection and treatment of AK lesions.

"Since it's not possible to predict exactly which actinic keratoses will advance to skin cancer, early detection and treatment of lesions are critical," says Dr. Robert Bissonnette, consultant dermatologist, Hôpital régional de Baie-Comeau. "Studies such as the ones involving ingenol mebutate certainly show promise as an effective new AK treatment option, but we still need to remain focused on behavioural interventions that could prevent the problems in the first place."

ABOUT ACTINIC KERATOSIS

Actinic keratoses are common, pre-malignant skin lesions caused by long-term UV exposure (usually from the sun). AK lesions are often red, scaly and may initially be mistaken for a rash or other skin irritation.

Studies show that 60 to 80 per cent of SCC cases begin as AK,4,5 and patients with AK are six times more likely to develop any type of skin cancer than people without it.6,7 In fact, AK is now considered by some authorities to be an in situ SCC, or a form of tumour at the beginning of a process of cancer development.8,9

The number of AK patients is both large and rapidly growing; the incidence of AK has increased worldwide,10 especially in areas where the UV index continues to increase, including Canada. Those at high-risk are often over age 40 and tend to have fair skin and a history of cumulative sun exposure.11

Both health care professionals and the general population have a role to play in AK prevention. Primary care practitioners need to take a more active role in counseling on sun safety and performing skin screenings of patients, looking for the specific signs of actinic keratosis. Members of the general population need to practice sun safety, and perform their own regular skin checks.

ABOUT THE STUDIES

Face and Scalp Data

Two of the studies compared ingenol mebutate 0.015 per cent to a placebo (vehicle) applied once-daily for three consecutive days to AK on the face or scalp. In the first study, after 57 days (about eight weeks), complete clearance of AK lesions occurred in 47 per cent (67/142) of patients using ingenol mebutate and five per cent (7/136) of patients using placebo (P<0.001). The median reduction in total number of lesions from baseline was 87 per cent.12 The second study found complete clearance in 37 per cent (50/135) of patients in the ingenol mebutate group and 2 per cent (3/134) of patients in the vehicle group (P<0.001).13

The most frequently reported local skin responses in the face and scalp studies were erythema (redness), flaking/scaling and crusting, which peaked on day four and returned to below baseline by day 29.12 The most common treatment-related adverse events were mild or moderate application-site reactions of pain 19 per cent (25/132) and pruritus 11 per cent (14/132); two per cent of patients (3) experienced adverse events classified as severe. Treatment adherence was high; 99 per cent and 96 per cent of patients in the active treatment group completed therapy in the respective studies.13 Both studies were funded by LEO Pharma and included centres in the United States and Australia.

Body Data

The other two studies compared ingenol mebutate 0.05 per cent to a placebo gel (vehicle) applied once-daily for two consecutive days to actinic keratoses on the body (arm, chest, back of the hand, leg, back or shoulder). In the first study, after 57 days, complete clearance of AK lesions occurred in 28 per cent (35/126) of patients using ingenol mebutate and five per cent (6/129) of patients using placebo (P<0.0001).14 The second study found complete clearance of AK lesions in 42 per cent of patients in the ingenol mebutate group and five per cent of patients in the vehicle group (P<0.001). The median reduction in total number of lesions from baseline was 75 per cent.15

The most frequently reported local skin responses in the body studies were erythema (redness) and flaking/scaling, which peaked between days three and eight and returned to baseline at day 57.14, 15 Adverse events were generally mild to moderate and resolved by day 57.14 The most common treatment-related adverse events were application-site irritation and itching.14 All local skin responses and treatment-related application-site adverse reactions resolved without sequelae.15 Both studies were funded by LEO Pharma and included centres in the United States and Australia. Ingenol mebutate is a topical gel derived from the Euphorbia peplus plant, and is being studied for its effect on AK.

ABOUT LEO PHARMA INC.

The LEO head office in Canada is located in Thornhill, Ontario, and is an integrated part of almost 4,000 employees in 40 countries. The Canadian operation covers R&D, Sales/Marketing and Administration functions. One-third of LEO personnel are employed in R&D. Established since 1983, LEO Pharma Inc.(Canada) has grown to become the fourth largest LEO healthcare sales/marketing operation internationally and a major contributor in the LEO global clinical development program. For more information about LEO Pharma in Canada, please visit www.LEOPharma.ca<http://www.LEOPharma.ca>.

References:

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1 What Are Actinic Keratoses? ActinicKeratoses.net. Available at: http://www.skincarephysicians.com/actinickeratosesnet/whatare.html. Accessed April 8, 2011.

2 Lansbury L, Leonardi-Bee J, Perkins W, et al. The Cochrane Collaboration, p. 4.

3 National Skin Cancer Prevention Committee. The economic burden of skin cancer in canada: current and projected. February 26, 2010, p. 1 and 42.

4 Berner A. Actinic keratosis and development of cutaneous squamous cell carcinoma. Tidsskr Nor Laegeforen. 2005;125:1653-1654.

5 Mittelbronn MA, Mullins DL, Ramos-Caro FA, Flowers FP. Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma. Int J Dermatol. 1998;37:677-681.

6 What You Need To Know About™ Melanoma and Other Skin Cancer. National Cancer Institute. Available at http://www.cancer.gov/cancertopics/wyntk/skin. Accessed May 3, 2011.

7 What Are Basal and Squamous Cell Skin Cancers? American Cancer Society. Available at: http://www.cancer.org/Cancer/SkinCancer-BasalandSquamousCell/DetailedGuide/skin-cancer-basal-and-squamous-cell-what-is-basal-and-squamous-cell. Accessed May 3, 2011.

8 Roewert-Huber J, Stockfleth E, Kerl H. Pathology and pathobiology of actinic (solar) keratosis - an update. British Journal of Dermatology. 2007;157 Suppl 2:18-20.

9 Ackerman AB, Mones JM. Solar. Actinic keratosis is squamous cell carcinoma. British Journal of Dermatology. 2006;155(1):9-22.

10 Ulrich et al. Emerging Drugs for Actinic Keratosis. Expert Opinion on Emerging Drugs. 2010;15(4).

11 Ko CJ. AK Facts and controversies. Clinics in Derm. 2010; 28:249-253.

12 Lebwohl M. A randomized, parallel-group, double-blind, vehicle-controlled, multicenter study of the efficacy and safety of PEP005 (ingenol mebutate) gel, 0.015%, in patients with actinic keratoses on the head. Poster session presented at the 22nd World Congress of Dermatology meeting.

13 Berman B. A multicenter, randomized, parallel-group, double-blind, vehicle-controlled evaluation of the efficacy and safety of PEP005 (ingenol mebutate) Gel, 0.015%, in patients with actinic keratoses on the head (face or scalp). Poster session presented at the 22nd World Congress of Dermatology meeting.

14 Swanson N. A multicenter, randomized, parallel-group, double-blind, vehicle-controlled study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) gel, 0.05% in patients with actinic keratoses on non-head locations. Poster session presented at the 22nd World Congress of Dermatology meeting.

15 Anderson L. Multicenter, randomized, parallel-group, double-blind, vehicle-controlled phase III study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) Gel, 0.05%, in patients with actinic keratoses on non-head locations. Poster session presented at the 22nd World Congress of Dermatology meeting.

For further information:

FOR MORE INFORMATION ABOUT THIS RELEASE, OR TO SPEAK TO A DERMATOLOGIST OR THE CANADIAN SKIN PATIENT ALLIANCE, PLEASE CONTACT:

Vanessa Principe Edelman 416.849.8931 Vanessa.Principe@Edelman.com

Posted: June 2011

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