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 -

- 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.

(Logo: www.newscom.com/cgi-bin/prnh/20110606/460992 )

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 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.

    Media Contact
    Helga Heyn
    External Relations Manager
    Tel.: +45-26-29-41-97
    E-mail: helga.heyn@leo-pharma.com

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