Data Published in JAMA Dermatology Show Long-term Effectiveness of Ingenol Mebutate in Treating Actinic Keratosis (AK)

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LEO Pharma A/S

20 Mar, 2013, 23:47 GMT

PRINCES RISBOROUGH, England, March 20, 2013 /PRNewswire/ --

Two or three day treatment provides clinically relevant sustained clearance of AK after 12 months[1]

Results of long-term clearance rates of actinic keratosis (AK) lesions after treatment with ingenol mebutate gel are 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, it has been shown in the New England Journal of Medicine that ingenol mebutate effectively clears AK lesions after a two or three day treatment of an area 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, also experience sustained clearance of actinic keratosis lesions one year later.[1]

The primary outcome of the study showed that patients showing sustained complete clearance at 12 months, was 46 per cent (n=108) on the face and scalp and 44 per cent (n=76) on the trunk or extremities. The secondary outcome showed that patients in the overall population experienced approximately 87 per cent reduction in the original number of actinic keratoses in the treated area of skin.[1]

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

"Ingenol mebutate gel applied as field therapy for two or three consecutive days produced clinically relevant sustained clearance and long-term lesion reduction."[1]

Commenting on the results, Dr John Lear, Consultant Dermatologist at the Manchester Royal Infirmary said: "These results are positive news for patients. Not only does ingenol mebutate gel offer the shortest duration patient applied treatment available for actinic keratosis (at two or three days), with high adherence levels (over 98 per cent), the data also provides clear evidence for long-term effectiveness as clearance is sustained at 12 months."

Geraldine Murphy, Managing Director of LEO UK/IE, commented, "This data is another step forward towards our goal at LEO of providing both convenient and effective solutions to help people achieve healthy skin. Actinic keratosis can lead to non-melanoma skin cancer and is a growing problem throughout the world."

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]

Every year there are more new cases of skin cancer in the UK than breast and lung cancers combined.[5]  In the UK, one in five patients over the age of 60 have one or more actinic keratosis lesions.[6]

Ingenol mebutate gel is available in two different concentrations. For treatment of the face or scalp, the gel is applied at a concentration of 150mcg/g once daily, and treatment is completed in three consecutive days. For treatment of the trunk or extremities, the gel is applied once daily for two consecutive days at a concentration of 500mcg/g.[7]

Ingenol mebutate gel was approved by the US Food and Drug Administration (FDA) in January 2012;  by the Therapeutic Goods Administration (TGA) in Australia and European Commission (EC) in Europe in November 2012.

About Picato®

  • Picato® (ingenol mebutate) gel, is a new once-daily field treatment for actinic keratosis, it is a topical patient-applied treatment with an onset of action within hours.[8]    
  • Picato® is a field directed therapy, which treats actinic keratosis lesions within the treatment area, in two or three days[2],[ 7], the shortest duration when compared to weeks or months with other actinic keratosis patient-applied treatments.[9]-[12]
  • Adherence to Picato® in clinical trials was high at over 98 per cent, and is possibly due to the short duration of treatment.[2] Current patient-applied therapies have treatment durations from three weeks up to 90 days [2],[ 9]-[12], and associated with levels of patient adherence as low as 37 per cent.[13]*
  • In a recent survey, over 70 per cent of patients indicated that they found Picato® "very easy to use".[14]**
  • Picato® has been developed as a new treatment for actinic keratosis following an extensive and complex manufacturing and clinical programme over many years.  
  • The European Commission granted marketing authorisation for Picato® in Europe on 15 November 2012.
  • The efficacy and safety of Picato® was determined in four multicentre, randomised, double-blind, vehicle-controlled phase III studies.

Results:

  • Following once daily treatment for three consecutive days with Picato® 150mcg/g, complete clearance of face or scalp actinic keratosis in a 25cm[2] treatment area was achieved in 42.2 per cent of patients, with an 83 per cent median reduction in the number of lesions compared to baseline, when measured at Day 57.[2]
  • Following once daily treatment for two consecutive days with Picato® 500mcg/g, complete clearance of trunk or extremities actinic keratosis in a 25cm[2] treatment area was achieved in a third (34.1 per cent) of patients, with a 75 per cent median reduction in the number of lesions compared to baseline, when measured at Day 57.[2]

About actinic keratoses

  • Actinic keratosis (AK), also known as ‛solar keratosis', is a common sun-induced skin lesion[3], that is often a red, scaly patch that is not always easy to see[16] and may be pre-cancerous.[17]
  • Actinic keratosis can be found as a single lesion or patch, and can commonly affect an area of skin (known as ‛the field')[18]  particularly on parts of the body that are regularly exposed to the sun, such as the face, neck, scalp and ears.[19]
  • Actinic keratoses are common pre-malignant lesions, affecting up to 23 per cent of the British population aged 60+ years. [20],[ 21]
  • People who have fair-skin, burn easily in the sun, use sunbeds or have spent a lot of time outdoors are particularly at risk of solar keratosis.[22]
  • Every year there are more new cases of skin cancer in the UK than breast and lung cancers combined.[5]
  • There are two different types of skin cancer, some related to moles, melanomas[23], but others are not, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).[3]  Both types of skin cancer are linked to too much sun exposure and both can be dangerous for your health.[24]
  • Actinic keratosis may progress to non-melanoma skin cancer including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).
  • Studies have shown that:
  • 65 per cent of SCCs arise from actinic keratosis lesions;[8],[ 25]
  • eight per cent of actinic keratoses progress to SCCs per year (estimated average);[26]
  • there is no way to predict which actinic keratoses will progress to SCCs;[27] and
  • the risk of progression to SCC increases with the number of lesions present.[28]
  • Studies have also shown that people with actinic keratosis are approximately five times more likely to develop head and neck melanoma than those without.[29]

About LEO

  • Founded in 1908, LEO is an independent, research-based pharmaceutical company.
  • LEO 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 is headquartered in Denmark and is wholly owned by the LEO Foundation.
  • LEO has focused on dermatology for over 50 years and developed a broad portfolio of solutions for patients with actinic keratosis, psoriasis, eczema and other skin diseases.
  • LEO is developing a Patient Support Programme to answer questions that patients may have regarding their treatment. This is called QualityCare™. A free and confidential nurse helpline is available on 0800 090 2165.
  • LEO UK was established in 1960. Based in Princes Risborough, Buckinghamshire, the company employs approximately 240 people in Commercial, Sales, Marketing, Medical, Clinical Operations, Biometrics and Business Support Services. In the UK, LEO markets prescription only medicines with a focus on treating skin conditions such as psoriasis and infected eczema, as well as blood clots. For more information about LEO, visit http://www.leo-pharma.co.uk.

*Adherence and health-related quality of life in patients with Actinic Keratosis Survey - Executive Summary and Full Report prepared by Hamell Communications, 2012. Overall, 63.3% (193/305) of patients were non-adherent to their AK medication. The percentage of patients who were non-adherent to their treatment rose from 52.4% (66/126) for a treatment duration of 3-4 weeks, to 71.3% (107/150) for a treatment duration of 6-12 weeks.

** The Picato® Experience Program survey, sponsored by LEO Pharma Inc., is a brief survey to evaluate patient satisfaction with the Picato® treatment regimen. More than two-thirds (70.3 per cent) of patients indicated that Picato® was very easy to use.

References

1. Lebwohl M et al. JAMA Dermatology; Article in press.

2. Lebwohl M et al. N Eng J Med. 2012; 366:1010-9

3. Cohen J. J Clin Aesthet Dermatol. 2010; 3:39-44

4. Ulrich M et al. Expert Opinion. 2010; 15:545 - 55

5. Skin Cancer UK. Skin cancer in the UK: the facts. Available at  http://www.skcin.org/Documents/SCUK-DOWNLOAD-VERSION-(1). [Last accessed Dec 2012]

6. Bonerandi B, Caquant et al. JEADV. 2011; 25:1-51

7. [SmPC150] LEO Pharma. Picato® 150 mcg/g (ingenol mebutate) gel Summary of Product Characteristics. November 2012.

[SmPC500] LEO Pharma. Picato® 500 mcg/g (ingenol mebutate) gel Summary of Product Characteristics. November 2012. Available at  http://www.medicines.org.uk.

8. Berman B et al. Expert Opin. Pharmacother. 2009; 10:3015-31

9. [SmPC] Almirall. Solaraze® (Diclofenac) Summary of Product Characteristics. Available at  http://www.medicines.org.uk. [Last accessed March 2013]

10. [SmPC] Almirall. Actikerall® (Fluorouracil/Salicylic Acid) Summary of Product Characteristics. August 2011. Available at  http://www.medicines.org.uk. [Last accessed March 2013]

11. [SmPC] Meda Pharmaceuticals. Efudix® (Fluorouracil) Summary of Product Characteristics. Available at  http://www.medicines.org.uk. [Last accessed March 2013]

12. [SmPC] Meda Pharmaceuticals. Aldara® (imiquimod) Summary of Product Characteristics. Available at  http://www.medicines.org.uk. [Last accessed March 2013]

13. Data on File AK-001 Hamell Market Research. 2012;

14. Zografos P and Goncalves J. Poster presented at Maui Derm Conference, Hawaii: Experiences of patients treated with Picato® (ingenol mebutate) gel 0.015% for actinic keratosis of the face or scalp, 2013.

15. Gold S et al. Poster presented at AAD Conference 2012: Long-term follow up studies of ingenol mebutate gel for treatment of actinic keratosis, 2012.

16. Primary Care Dermatology Society. Actinic keratosis. Available at  http://www.pcds.org.uk/component/content/article/50-image-atlas-detailed-articles/73-actinic-keratosis. [Last accessed March 2013]

17. Quaedvlieg PJF et al. Eur J Dermatol. 2006; 16:335-9

18. Stockfleth E and Kerl H. Eur J Dermatol. 2006; 16:599-606

19. Goldberg L and Mamelak A. Journal of drugs in Dermatology. 2010; 9:1125-32

20. Memon A et al. Br J Dermatol. 2000; 142:1154-9

21. Harvey I et al. Br J Cancer. 1996; 74:1302-7

22. Berman B et al. Supplement to: The Journal of Family Practice. May 2006;1-8

23. BBC. Health - Skin Cancer. Available at  http://www.bbc.co.uk/health/physical_health/conditions/in_depth/cancer/skincancer1.shtml. [Last accessed Dec 2011]

24. Cancer Research UK. Skin Cancer - Key Facts. Available at http://info.cancerresearchuk.org/prod_consump/groups/cr_common/@nre/@sta/documents/generalcontent/cr_077225.pdf. [Last accessed March  2013]

25. Criscione VD et al. Cancer. 2009; 115:2523 - 30

26. Glogau R. Dermatol. 2000; 42:S23-4

27. Cockerell C. J Am Acad Dermatol. 2000; 42:S11-S7

28. Green A and Battistutta D. Int J Cancer. 1990; 46:356-61

29. Olsen C et al. Int J Cancer. 2011; 129:713-23