Four Phase 3 Efficacy and Safety Studies of Ingenol Mebutate, an Investigational Treatment for Actinic Keratosis, Presented at World Congress of Dermatology

COPENHAGEN, Denmark, June 6, 2011 /PRNewswire/ --

- NOT INTENDED FOR US MEDIA

- Ingenol Mebutate is an Investigational Two-to-Three Day Topical Treatment for Precancerous Skin Disease

Clinical data from four Phase 3 studies of ingenol mebutate gel, an investigational treatment for actinic keratosis, were presented publicly for the first time at the 22nd World Congress of Dermatology in Seoul. Two of the studies 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 keratoses at the day 57 visit.

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Actinic keratosis, caused by long-term UV exposure, is a precancerous skin condition, which can lead to squamous cell carcinoma, a non-melanoma form of skin cancer. "Since there is no way to predict which actinic keratoses will advance to skin cancer, early detection and treatment of lesions is critical," said Mark Lebwohl, M.D., Professor and Chair, Department of Dermatology, Mount Sinai Medical Center in New York.

Face and Scalp Data

Two of the studies compared ingenol mebutate 0.015% to a placebo (vehicle) applied once daily for three consecutive days to actinic keratoses on the face or scalp. In the first study, after 57 days (about 8 weeks), complete clearance of actinic keratosis lesions occurred in 47% (67/142) of patients using ingenol mebutate and 5% (7/136) of patients using placebo (P<0.001). The median reduction in total number of lesions from baseline was 87%.[1] The second study found complete clearance in 37% (50/135) of patients in the ingenol mebutate group and 2% (3/134) of patients in the vehicle group (P<0.001).[2]

The most frequently reported local skin responses in the face and scalp studies were erythema (redness), flaking/scaling, and crusting, which peaked on day 4 and returned to below baseline by day 29; [1]. The most common treatment related adverse events were mild or moderate application-site reactions of pain 19% (25/132) and pruritus 11% (14/132); 2% of patients (3) experienced adverse events classified as severe. Treatment adherence was high; 99% and 96% of patients in the active treatment group completed therapy in the respective studies [1],[2].

Body Data

The other two studies compared ingenol mebutate 0.05% 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 actinic keratosis lesions occurred in 28% (35/126) of patients using ingenol mebutate and 5% (6/129) of patients using placebo (P<0.0001).[3] The second study found complete clearance of actinic keratosis lesions in 42% (42/100) of patients in the ingenol mebutate group and 5% (5/103) of patients in the vehicle group (P<0.001).[4]

The most frequently reported local skin responses in the body studies were erythema (redness) and flaking/scaling, which peaked between days 3 and 8 returning to baseline at day 57[3],[4]. Adverse events were generally mild to moderate resolving by day 57[3]. The most common treatment related adverse events were application-site irritation and itching[3]. All local skin responses and treatment-related application-site adverse events resolved without sequelae[4].

About Ingenol Mebutate

Ingenol mebutate is a topical gel derived from the Euphorbia peplus plant, and is being studied for its effect on actinic keratosis. Data from the four studies were submitted to the United States Food and Drug Administration (FDA) as part of the New Drug Application (NDA) by LEO Pharma.

About Actinic Keratosis

Actinic keratoses are common skin lesions caused by long term UV exposure (usually from the sun). Actinic keratoses are often red, scaly and may initially be mistaken for a rash or other skin irritation, but do not improve over time. The number of actinic keratosis patients is both large and rapidly growing, with the American Academy of Dermatology estimating that 60 percent of predisposed persons older than 40 have at least one actinic keratosis.[5] People at high-risk are often over age 40 and tend to have fair skin and a history of cumulative sun exposure.[6] Actinic keratosis is often considered to be the earliest stage in the development of skin cancer, with the potential to progress to squamous cell carcinoma, a non-melanoma cancer which is the second most common type of skin cancer. Studies show that 60-80 percent of squamous cell carcinoma cases begin as actinic keratosis,[7] and patients with the condition are six times more likely to develop any type of skin cancer than people without it. [8]

About LEO Pharma

Founded in 1908, LEO Pharma is a global independent, research-based pharmaceutical company. LEO Pharma is committed to the discovery and development of novel drugs for patients within the areas of dermatology and critical care medicine. LEO Pharma has its own sales forces in 58 countries and employs more than 3,900 employees worldwide. For more information about LEO Pharma, visit http://www.leo-pharma.com.

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[1] 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. 22nd World Congress of Dermatology. Abstract P2181.

[2] 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). 22nd World Congress of Dermatology. Abstract P2179.

[3] 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. 22nd World Congress of Dermatology. Abstract P2182.

[4] 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. 22nd Congress of Dermatology. Abstract P2180.

[5] Drake LA, Ceilley RI, Cornelison RL, et al. Guidelines of care for actinic keratoses. Committee on Guidelines of Care. J Am Acad Dermatol 1995;32:95-8.

[6] Ko CJ. AK Facts and controversies. Clinics in derm. 2010; 28:249-253

[7] 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.

[8] Chen GJ, Feldman SR, Williford PM, et al. Clinical diagnosis of actinic keratosis identifies an elderly population at high risk of developing skin cancer. Dermatol Surg. 2005;31:43-47.

    
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