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New England Journal of Medicine Article Reviews the Benefits of Ingenol Mebutate in Field Treatment of Actinic Keratoses

PARSIPPANY, New Jersey, March 14, 2012 /PRNewswire/ --

Ingenol mebutate was proven efficacious with a once-daily application for only 2 or 3 days

Today, the New England Journal of Medicine (NEJM) published an analysis of pooled results from LEO Pharma's four Phase III clinical trials for ingenol mebutate gel, demonstrating that ingenol mebutate gel is safe and effective for the treatment of actinic keratoses (AKs) on the trunk-extremities or face-scalp with only 2 or 3 days use, respectively.[1]


Ingenol mebutate gel, marketed in the US as Picato®, is a new topical gel for the treatment of actinic keratosis. Actinic keratoses can be considered a precursor to squamous cell carcinoma (SCC).[3]The authors of this publication concluded that with a once-daily treatment for only 2 or 3 consecutive days, ingenol mebutate gel will provide physicians with an effective new option for the treatment of actinic keratosis.

The authors of the article, Ingenol Mebutate Gel for Actinic Keratosis, reported, "Two clear benefits are derived from the short exposure to ingenol mebutate."  The article explains that the short 2- or 3-day dosing combined with the rapid resolution of local skin responses (LSRs) may benefit patients.   

Lead author Mark Lebwohl, M.D., Professor and Chair, Department of Dermatology, Mount Sinai Medical Center in New York, said: "In these Phase III trials, almost all patients completed the full course of treatment. The evidence provided by these controlled studies shows ingenol mebutate gel to be an effective treatment for AKs on the head or body."

Ingenol mebutate gel is a field-directed topical therapy that enables treatment of an area or field containing AKs on the head or body. In the pooled analysis of the face and scalp data in the New England Journal of Medicine publication, complete clearance of AKs was significantly higher in patients treated with ingenol mebutate gel at day 57 than compared to vehicle gel (42.2% vs. 3.7%, p<0.001). Similarly, in the pooled analysis of the trunk and extremities, complete clearance at day 57 was significantly higher after treatment with ingenol mebutate gel than compared to vehicle gel (34.1% vs. 4.7%, p<0.001).[1] Complete clearance was the primary end point in both studies and was defined as having no clinically apparent AK lesions in a contiguous 25 cm[2] studied treatment area.

Partial clearance on the face and scalp at day 57 (defined as a reduction of at least 75% of the number of clinically apparent AKs in the treatment area) was achieved in 63.9% of patients treated with ingenol mebutate gel compared to 7.4% of the vehicle gel group. In trunk and extremities studies, 49.1% of patients treated with ingenol mebutate gel achieved partial clearance compared to 6.9% of the vehicle gel group.

Patients experienced local skin responses of generally mild to moderate intensity which resolved rapidly, within 2 weeks for areas treated on the face and scalp, and within 4 weeks for areas treated on the trunk and extremities. The most common treatment-related adverse events in all studies were mild to moderate application site reactions (for face-scalp 19% vs. 2.6% in the vehicle gel group; for trunk-extremities 12% vs. 2.6% in the vehicle gel group). No treatment related serious adverse events were reported in the trials.[1]

Kim Kjoeller, Vice President, Research and Development, at LEO Pharma A/S stated, "The results of these studies are very encouraging and provide clear evidence for ingenol mebutate gel as an effective, short duration treatment for AK. These results underline the commitment of LEO Pharma to dermatological research and the development of treatments that improve patient outcomes."

"The acceptance and publication of these pivotal clinical trial results in the New England Journal of Medicine underscores the commitment of LEO Pharma to a high level of scientific excellence and the importance of this new therapeutic option for the millions of people suffering from AK in the US" said John Koconis, President and CEO of LEO Pharma Inc.

Ingenol mebutate gel was approved for the treatment of AK by the US Food and Drug Administration on January 23, 2012, and will be available in pharmacies by April 1st. 

About Picato® gel

Ingenol mebutate gel is available in two different concentrations: for treatment of the face and scalp, the gel is applied at a concentration of 0.015% once-daily for three consecutive days; whereas for treatment of the body, the gel is applied once-daily for two consecutive days at a concentration of 0.05%.

Important Safety Information

For topical use only; not for oral, ophthalmic, or intravaginal use. Eye disorders, including severe eye pain, eyelid edema, eyelid ptosis, periorbital edema can occur after exposure. Patients should wash hands well after applying Picato® gel, and avoid transfer of the drug to the periocular area during and after application. Severe skin reactions in the treated area, including erythema, crusting, swelling, vesiculation/pustulation, and erosion/ulceration, can occur after application. Administration of Picato® gel is not recommended until the skin is healed from any previous drug or surgical treatment. The most common adverse reactions observed in clinical trials (≥2%) are local skin reactions, application site pain, application site pruritus, application site irritation, application site infection, periorbital edema, nasopharyngitis and headache. There are no adequate and well-controlled studies of Picato® gel in pregnant women. Picato® gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The safety and effectiveness of Picato® gel for actinic keratosis in patients less than 18 years of age have not been established.

Please see full Prescribing Information available at:

About actinic keratoses

Actinic keratosis (AK) is a dry, scaly, rough-textured patch or lesion that forms on the outermost layer of the skin after cumulative exposure to ultraviolet (UV) light, such as sunlight. In some cases, the lesions may be easier to feel than see. The name actinic keratosis literally means "sun-induced rough spot" and therefore the lesions, which can be gray, pink, red or the same color as the skin, are often called sun spots and/or age spots.

A job that requires spending hours of time outside, or everyday activities such as gardening, exercise or attending outdoor sporting events, can lead to sun damage if skin isn't adequately protected. People at high risk are often fair-skinned men and women over the age of 40 who may have accumulated a significant amount of sun exposure over the course of many years.[2]

About LEO Pharma

Founded in 1908, LEO Pharma is an independent, research-based pharmaceutical company. LEO Pharma develops, manufactures and markets pharmaceutical drugs to dermatologic and thrombotic patients in more than 100 countries globally. The company has its own sales forces in 61 countries and employs more than 4,600 employees worldwide. LEO Pharma is headquartered in Denmark and is wholly owned by the LEO Foundation.


1. Lebwohl M et al, N Engl J Med 366; March 15, 2012.

2. "What Are Actinic Keratoses?" ActinicKeratosesNet. American Academy of Dermatology. Updated October 19, 2005.

Accessed December 1, 2011. <>

3.  Ko CJ. Actinic keratosis: facts and controversies. Clin Dermatol 2010;28(3):249-53.

For more information about LEO Pharma, visit



Posted: March 2012