Picato® Gel Receives EU Marketing Authorisation for Treatment of Actinic Keratosis

Ballerup, Denmark (ots/PRNewswire) -

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 2010;3(6):39-44.

2. Naldi L, Chatenoud L, Piccitto R, Colombo P, Placchesi EB, La
Vecchia C. Prevalence of actinic keratoses and associated factors in
a representative sample of the Italian adult population: Results from
the Prevalence of Actinic 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.

4. Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B.
Ingenol mebutate gel for actinic keratosis. N Engl J Med. Mar 15
2012;366(11):1010-1019.

5. Shoimer I, Rosen N, Muhn C. Current management of actinic
keratoses. Skin therapy letter. May 2010;15(5):5-7.

6. Yentzer B, Hick J, Williams L, et al. Adherence to a topical
regimen of 5-fluorouracil, 0.5%, cream for the treatment of actinic
keratoses. Arch Dermatol. Feb 2009;145(2):203-205.

7. Stockfleth E, Kerl H. Guidelines for the management of actinic
keratoses. Eur J Dermatol. Nov-Dec 2006;16(6):599-606.

8. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic
keratoses: Natural history and risk of malignant transformation in
the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer.
Jun 1 2009;115(11):2523-2530.

9. Cozzi SJ, Ogbourne SM, James C, et al. Ingenol mebutate
field-directed treatment of UVB-damaged skin reduces lesion formation
and removes mutant p53 patches. J Invest Dermatol. Apr
2012;132(4):1263-1271.

10. Ogbourne SM, Suhrbier A, Jones B, et al. Antitumor activity
of 3-ingenyl angelate: plasma membrane and mitochondrial disruption
and necrotic cell death. Cancer Res. Apr 15 2004;64(8):2833-2839.

11. Ulrich M, Drecoll U, Stockfleth E. Emerging drugs for actinic
keratosis. Expert Opin Emerg Drugs. Dec 2010;15(4):545-555.

12. Harvey I, Frankel S, Marks R, Shalom D, Nolan-Farrell M.
Non-melanoma skin cancer and solar keratoses. I. Methods and
descriptive results of the South Wales Skin Cancer Study. Br J
Cancer. Oct 1996;74(8):1302-1307.

13. Memon AA, Tomenson JA, Bothwell J, Friedmann PS. Prevalence
of solar damage and actinic keratosis in a Merseyside population. Br
J Dermatol. Jun 2000;142(6):1154-1159.

14. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ
transplantation. N Engl J Med. Apr 24 2003;348(17):1681-1691.

15. Mittelbronn MA, Mullins DL, Ramos-Caro FA, Flowers FP.
Frequency of pre-existing actinic keratosis in cutaneous squamous
cell carcinoma. Int J Dermatol. Sep 1998;37(9):677-681.

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.

18. Salasche SJ. Epidemiology of actinic keratoses and squamous
cell carcinoma. J Am Acad Dermatol. Jan 2000;42(1 Pt 2):4-7.

19. Stockfleth E. Topical management of actinic keratosis and
field cancerisation. G Ital Dermatol Venereol. Aug
2009;144(4):459-462.

20. 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. Jan 2005;31(1):43-47.

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ots Originaltext: LEO Pharma
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Contact:
Contact: Polly Lutter, Corporate External Relations Manager, LEO
Pharma, Email: polly.lutter@leo-pharma.com , Tel: +44(0)203-077-0499