Picato(R) Gel Receives EU Marketing Authorisation for Treatment of Actinic Keratosis

AsiaNet 51417

BALLERUP, Denmark, Nov. 19 /PRN=KYODO JBN/ --

Today LEO Pharma announced that the European Commission (EC) has granted

marketing authorisation for Picato(R) (ingenol mebutate) gel as a treatment for

actinic keratosis in the European Union (EU). Picato(R) gel is a once-daily,

two or three day field-directed topical treatment for actinic keratosis, a

common skin condition which if not treated can lead to squamous cell carcinoma,

a form of non-melanoma skin cancer.[1]

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Actinic keratosis can be an under-diagnosed condition,[2] yet the prevalence in

adults aged over 40 years ranges between 11-25 per cent in susceptible

populations of the northern hemisphere, and between 40-60 per cent in the

southern hemisphere.[3] Current topical treatments have long treatment

durations that last for periods from one, up to four months, which can lead to

low patient adherence.[4-6]

Professor Eggert Stockfleth, Head of Dermatology at the Skin Centre Charite

Hospital in Berlin, Germany and Head of the European Skin Cancer Foundation

(ESCF), commented:

"Since it is impossible to predict which actinic keratosis lesions will advance

to non-melanoma skin cancer, early detection and effective treatment is

critical. What makes Picato(R) gel a particularly appealing product is the

short treatment duration needed to treat actinic keratosis. This short duration

- just two or three days - should lead to higher patient adherence. In clinical

trials adherence was as high as 98 per cent."

Actinic keratoses often appear as red, scaly lesions predominantly seen on skin

frequently exposed to the sun, such as the face, head, arms and legs. They can

occur as single lesions or multiple lesions affecting an area of skin (a

'field').[7] Actinic keratoses can lead to squamous cell carcinoma - in fact,

research shows 65 per cent of squamous cell carcinomas arise from lesions

previously diagnosed as actinic keratoses.[8]

Picato(R) gel is indicated for the cutaneous treatment of adult patients with

non-hyperkeratotic, non-hypertrophic actinic keratosis. Picato(R) gel treats

actinic keratoses over a limited area (field) of sun-damaged skin. Picato(R)

gel is available in two different dosage strengths for treatment of specific

areas of the body. For treatment of the face and scalp, Picato(R) gel is

applied at a concentration of 150 mcg/g once daily for three consecutive days.

For treatment of the trunk and extremities, the gel is applied at a

concentration of 500 mcg/g once daily for two consecutive days.

Gitte P. Aabo, Chief Executive Officer (CEO) of LEO Pharma, commented:

"Actinic keratosis is a growing problem across the world, yet many patients do

not recognise their symptoms or the significance of them, unaware that lesions

can in some cases develop into non-melanoma skin cancer. Picato(R) gel requires

just two or three consecutive days of treatment, compared to several weeks or

months for existing topical therapies. Following approval in the US, the

approval of Picato(R) gel in the EU is another important step in our goal of

helping people across the world achieve healthy skin."

Picato(R) 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 in November 2012.

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 25cm2 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.[4]

- 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.[9,10] 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.

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.

- There is no relevant use of Picato(R) gel in the paediatric population.

- Please see full prescribing information available at

http://www.leo-pharma.com.

About actinic keratoses

- 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.[11] In the UK, around 3.6 per cent of men aged

between 40 and 49 years, and 20 per cent of patients over 60 years, have at

least one actinic keratosis lesion.[12,13]

- 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.[14]

- Actinic keratoses are considered by some to be the earliest stage in the

development of non-melanoma 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.[15,16]

- After receiving a diagnosis of actinic keratosis, the risk of developing

squamous cell carcinoma over a ten year period is approximately ten per cent

for a patient having an average of 7.7 actinic keratosis lesions[16-18] and it

is impossible to predict which lesions will develop into skin cancer.[19]

- A study has shown that around 65 per cent of squamous cell carcinoma cases

may begin as actinic keratoses[8] and patients with the condition are six times

more likely to develop any type of skin cancer than people without it.[20]

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 around 5,000

people worldwide.

- LEO Pharma is headquartered in Denmark and is wholly owned by the LEO

Foundation.

- For more information about LEO Pharma, visit http://www.leo-pharma.com.

References

1.    Cohen JL. Actinic keratosis treatment as a key component of preventive

strategies for nonmelanoma skin cancer. J Clin Aesthet Dermatol. Jun

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2.    Naldi L, Chatenoud L, Piccitto R, Colombo P, Placchesi EB, La Vecchia C.

Prevalence of actinic keratoses and associated factors in a representative

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Keratoses Italian Study, 2003-2004. Arch Dermatol. Jun 2006;142(6):722-726.

3.    Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. Oct

1994;131(4):455-464.

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15.    Mittelbronn MA, Mullins DL, Ramos-Caro FA, Flowers FP. Frequency of

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16.    Berman B, Amini S, Valins W, Block S. Pharmacotherapy of actinic

keratosis. Expert Opin Pharmacother. Dec 2009;10(18):3015-3031.

17.    Dodson JM, DeSpain J, Hewett JE, Clark DP. Malignant potential of

actinic keratoses and the controversy over treatment. A patient-oriented

perspective. Arch Dermatol. Jul 1991;127(7):1029-1031.

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SOURCE: LEO Pharma A/S