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

Ballerup, Denmark (ots/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/20130221/595427 )

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]

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,[8],[10],[11] and it is impossible to
predict which lesions will develop into skin cancer.[12]

A study has shown that around between 40-80 per cent of squamous
cell carcinoma cases may begin as actinic keratoses,[8],[13],[14] and
patients with the condition are six times more likely to develop any
type of skin cancer than people without it.[15]

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) Lebwohl M, Shumack, S et al., Long-Term Follow-up of Ingenol Mebutate Gel
for the Treatment of Actinic Keratosis JAMA Dermatology; Article in press
2) 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
3) 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.
4) Ulrich M, Drecoll U, Stockfleth E. Emerging drugs for actinic keratosis.
Expert Opin Emerg Drugs. Dec 2010;15(4):545-555.
5) 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.
6) 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.
7) Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N
Engl J Med. Apr 24 2003;348(17):1681-1691.
8) 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.
9) Berman B, Amini S, Valins W, Block S. Pharmacotherapy of actinic keratosis.
Expert Opin Pharmacother. Dec 2009;10(18):3015-3031.
10) 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.
11) Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma.
J Am Acad Dermatol. Jan 2000;42(1 Pt 2):4-7.
12) Stockfleth E. Topical management of actinic keratosis and field
cancerisation. G Ital Dermatol Venereol. Aug 2009;144(4):459-462.
13) Feldman SR, Fleischer AB, Jr. Progression of actinic keratosis to squamous
cell carcinoma revisited: clinical and treatment implications. Cutis 2011;87(4):201-7.
14) Dinehart, Nelson-Adesokan, Cockerell, Russell, Brown. Metastatic cutaneous
squamous cell carcinoma derived from actinic keratosis. Cancer 1997; 79(5):920-3.
15) 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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http://photos.prnewswire.com/prnh/20130221/595427

ots Originaltext: LEO Pharma
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Contact:
Global Contact: Polly Lutter, Global External Relations Manager,
LEO Pharma A/S, Email: polly.lutter@leo-pharma.com , +44 (0) 20 7300
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