Article Published in JAMA Dermatology Shows Long-term Effectiveness of Ingenol Mebutate in Treating Actinic Keratosis (1

BALLERUP, Denmark, March 20, 2013 /PRNewswire/ --

Two-three day treatment provides clinically relevant, sustained clearance of AK after 12 months

An analysis of long-term clearance rates of actinic keratosis (AK) lesions after treatment with ingenol mebutate (Picato(R)) gel is today published in the Journal of the American Medical Association (JAMA) Dermatology,[1] formerly known as the Archives of Dermatology.

(Photo: http://photos.prnewswire.com/prnh/201302... )

Previously, the pooled results of the four phase III trials of ingenol mebutate published in the New England Journal of Medicine (NEJM) showed that ingenol mebutate gel effectively clears AK lesions after a two or three day topical treatment of an area of skin (also known as a field).[2]

The current data in JAMA Dermatology show that patients who achieved complete clearance after initial treatment with ingenol mebutate gel, also experience sustained clearance of AK lesions one year later.[1]

The primary outcome of the study showed that patients showing sustained complete clearance at 12 months, was 46% on the face and scalp and 44% on the trunk or extremities. The secondary outcome showed that patients in the overall population experienced approximately 87% reduction in the original number of actinic keratoses in the treated area of skin.[1]

The authors of the article 'Long-Term Follow-up of Ingenol Mebutate Gel for the Treatment of Actinic Keratosis' concluded:

"Ingenol mebutate gel applied as field therapy for only two or three consecutive daily doses was effective when treating head or body actinic keratoses, producing clinically relevant sustained clearance and long-term reduction in lesions."[1]

Author Dr Stephen Shumack, a Consultant Dermatologist from Sydney's Royal North Shore Hospital, Australia, commented:

"These long-term data are encouraging for patients with actinic keratosis. It has now been demonstrated that once daily, two or three day treatment with ingenol mebutate gel leads to a reduction in the number of actinic keratoses present after 12 months, compared to the number seen at baseline. These results are comparable to those seen with other topical therapies with longer treatment durations.[1]These data show long-term effectiveness combined with short duration of treatment, offering a significant benefit to patients living with actinic keratosis."

Dr Kim Kjoller, Senior Vice President of Global Development at LEO, said:

"These data provide clear evidence that ingenol mebutate gel is effective in sustaining long-term clearance of actinic keratoses. The short duration of treatment required for ingenol mebutate is an important step in providing convenient and effective solutions to treat this widespread condition."

Actinic keratoses are rough skin lesions caused by cumulative exposure to the sun, which can potentially lead to non-melanoma skin cancer (NMSC) if not treated early and effectively.[3] The majority of lesions are caused by long-term sun exposure in fair-skinned people. The number of patients with actinic keratosis is rapidly growing, especially in Europe, the US and Australia.[4]

Ingenol mebutate gel is available in two different concentrations. For treatment of the face and scalp, ingenol mebutate gel is applied at a concentration of 150 mcg/g over a 25 cm[2] area once daily for three consecutive days. For treatment of the body, ingenol mebutate gel is applied over a 25 cm[2] area once daily for two consecutive days at a concentration of 500 mcg/g.

Ingenol mebutate gel was approved by the US Food and Drug Administration (FDA) in January 2012; by the Agencia Nacional de Vigilancia Sanitaria (ANVISA) in Brazil in July 2012; and by the Therapeutic Goods Administration (TGA) in Australia, the European Commission (EC) in Europe in November 2012 and by Health Canada in January 2013.

About Picato(R) gel

Picato(R) gel is a topical, field-directed therapy which is self-administered by the patient to the affected areas of the skin once a day for two or three consecutive days, depending on the treatment area.

Picato(R) gel has two strengths and two application regimens to follow, dependent upon the location of the actinic keratoses. Picato(R) gel is applied over a 25cm[2] treatment area for two consecutive days when treating actinic keratoses on the trunk and extremities (500 mcg/g) and over three consecutive days for the face and scalp (150mcg/g).

Picato(R) gel has been shown in a large clinical trial programme to effectively clear actinic keratosis lesions on the face and scalp, as well as on the trunk and extremities.[2]

The mechanism of action (MoA) for Picato(R) gel is not fully understood. In vivo and in vitro data suggest a dual MoA, including direct lesional cell death and infiltration of immunocompetent cells.[5],[6]

Non-invasive examination of skin treated with Picato(R) gel showed an almost complete resolution of induced skin changes measured at two months post treatment, and patients treated with Picato(R) gel showed a higher treatment satisfaction than placebo-treated patients in clinical trials.[2]

Important product information

Contact with the eyes should be avoided. Eye disorders such as eye pain, eyelid oedema and periorbital oedema should be expected to occur after accidental eye exposure of Picato(R) gel.

Picato(R) gel must not be ingested.

Administration of Picato(R) gel is not recommended until the skin is healed from treatment with any previous medicinal product or surgical treatment and should not be applied to open wounds or damaged skin where the skin barrier is compromised.

Picato(R) gel should not be used near the eyes, on the inside of the nostrils, on the inside of the ears or on the lips.

Local skin responses such as erythema, flaking/scaling, and crusting should be expected to occur after cutaneous application of Picato(R) gel.

Due to the nature of the disease, excessive exposure to sunlight (including sunlamps and tanning beds) should be avoided or minimised.

Lesions clinically atypical for actinic keratosis or suspicious for malignancy should be biopsied to determine appropriate treatment.

There are no data from the use of ingenol mebutate in pregnant women. Risks to humans receiving cutaneous treatment with ingenol mebutate are considered unlikely as Picato(R) gel is not absorbed systemically. As a precautionary measure, it is preferable to avoid the use of Picato(R) gel during pregnancy.

Actinic keratosis is not a condition generally seen within the pediatric population. The safety and efficacy of Picato(R) gel for actinic keratosis in patients less than 18 years of age have not been established.

Please see full prescribing information available at http://www.leo-pharma.com.

About actinic keratosis (AK)

Actinic keratoses are skin lesions, which are often red, scaly and may initially be mistaken for a rash or other skin irritation. The majority of lesions are caused by sun exposure in fair-skinned people.

The number of patients with actinic keratosis is rapidly growing, especially in Europe, the US and Australia.[4]

Actinic keratoses are more common in males, and individuals with a fair skin type. Additional risk factors include advanced age and immunodeficiency. Immunocompromised patients have a 65 to 250 fold higher risk for actinic keratoses and invasive squamous cell carcinoma, which is a type of NMSC.[7]

Actinic keratosis is a precursor to non-melanoma skin cancer which is the second most common type of skin cancer. [8],[9]

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