3 days popular7 days popular1 month popular3 months popular

New Treatment For Actinic Keratosis Now Available In The UK

A new treatment for sun-damaged skin that can lead to skin cancer was launched recently by LEO Pharma.

Picato® (ingenol mebutate) gel is a topical treatment licensed for the cutaneous treatment of non- hyperkeratotic, non-hypertrophic actinic keratosis (AK) in adults, a type of skin damage caused by long-term sun, or UV exposure, that has the potential to progress to the non-melanoma skin cancer, squamous cell carcinoma (SCC).1, 2

Current topical, patient-applied therapies have treatment durations from three weeks up to three months 3-7, longer treatment durations can lead to levels of patient adherence as low as 37 per cent.8* Picato® effectively manages actinic keratosis with a once-daily treatment, which is applied over two or three days9 and demonstrates high patient adherence in clinical trials of over 98 per cent.9

Actinic keratosis often appears as red, rough, sandpapery patches of skin10 on areas that are more exposed to sun11, such as the face, head, arms and legs. It can occur as a single lesion or multiple lesions affecting an entire area (known as the ‘field’). Where there are multiple lesions, it is important to treat the entire field.12 Picato® is a field-directed topical gel, indicated for the treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults.13

An extensive phase III clinical trial programme has demonstrated that, three days’ treatment application with Picato® 150mcg/g on the face or scalp led to an 83 per cent median reduction in the number of AK lesions compared to baseline, when measured at Day 57.9 Following two days’ treatment application on the trunk or extremities with Picato® 500mcg/g, there was a 75 per cent median reduction in the number of AK lesions compared to baseline, when measured at Day 57.9

Commenting on the launch, Dr Tony Downs, Consultant Dermatologist, Royal Devon and Exeter Hospital, said, “The launch of Picato® in the UK is a very positive step forward for both patients living with actinic keratosis, and GPs and dermatologists treating the condition. As it is impossible to predict which actinic keratosis lesions will advance to non-melanoma skin cancer, early detection and effective treatment is very important.”

In March this year, the Scottish Medicines Consortium (SMC) accepted Picato® for use in Scotland (the full advice can be found at the end of this article).14 NICE recently published an Evidence Review Summary for ingenol mebutate gel (ESNM14) which recognised that the simple dosing regimen and the short duration of the treatment course compared with other self-applied, field- directed agents (with side effects peaking after treatment is completed) may be beneficial in terms of adherence to treatment.15

Dr Stephen Kownacki, Executive Chair of the Primary Care Dermatology Society (PCDS) said, “Actinic keratosis is a condition that in the majority of cases can be managed and treated effectively in primary care, avoiding unnecessary referrals. When treatment is needed, Picato® provides GPs and their patients with an effective and fast treatment to address this potentially pre-cancerous condition.”

Patients are likely to develop local skin responses (LSRs) following treatment with topical therapies for actinic keratosis. The development of LSRs following treatment with Picato® are typically of same day onset and predictable over time and typically resolve within two to four weeks depending on body location13 causing less inconvenience to the daily life of patients.

Dr Tony Downs added, “The key to effective actinic keratosis management is adherence to treatment. There is every reason that the high compliance levels seen in the clinical trials can be replicated in the primary care setting. Better compliance will result in the ultimate goal of improved outcomes for patients.”

Every year there are more new cases of skin cancer in the UK than breast and lung cancers combined.16 Worldwide, the number of patients with actinic keratosis is rapidly growing, especially in Europe, the US and Australia. In the UK, approximately one in five patients aged 60+ years have one or more actinic keratosis lesions.17

Charlotte Fionda, Director of Skcin, the UK’s only national skin cancer-specific charity, said, “Sadly, public awareness of the dangers of overexposure to UV light is very poor and the incidence of skin cancer and potential pre-cursors such as actinic keratosis is on the rise. It is now more important than ever for the general public to be skin savvy and check their skin for any changes.” Ingenol mebutate, the active ingredient in Picato® is derived from the sap of the plant Euphorbia peplus (also known as E. peplus). The product has been developed as a new treatment for actinic keratosis following an extensive and complex manufacturing and clinical programme over many years.

Geraldine Murphy, Managing Director of LEO Pharma UK/IE, commented, “LEO Pharma UK/IE is committed to providing total care solutions to people living with skin disease and the launch of Picato® in the UK and Ireland is a significant advance for patients suffering from actinic keratosis. Actinic keratosis can lead to non-melanoma skin cancer and is a growing problem throughout the world. This launch of Picato® in the UK is another step forward towards our goal of helping people achieve healthy skin.”

LEO Pharma is developing a Patient Support Programme to answer questions that patients may have regarding their condition and its treatment. This is called QualityCareTM. A free and confidential nurse supportline for Picato® patients is currently available on Tel: 0800 090 2165. This programme will later include a website for all AK patients.

The advice from the SMC on Picato® is:
ADVICE: following a full submission, ingenol mebutate (Picato®) is accepted for use within NHS Scotland.
Indication under review: Cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults.
In four randomised, double-blind, phase III studies, a significantly greater proportion of adults with actinic keratosis (AK) achieved complete clearance when treated with ingenol mebutate gel compared with vehicle control.
The full guidance from the SMC on ingenol mebutate may be found at:
http://www.scottishmedicines.org.uk/SMC_Advice/Briefing_Note/2013

About Picato® 

Picato® (ingenol mebutate) gel, is indicated for the cutaneous treatment of non- hyperkeratotic, non-hypertrophic actinic keratosis in adults.13

The gel, is a new once-daily field treatment for certain types of actinic keratosis, it is a topical, patient-applied treatment with an onset of action within hours.18

It is a field directed therapy, which means that it treats a number of actinic keratosis lesions within a treatment area. It is applied on two or three days9, 13, the shortest duration when compared to weeks or months with other actinic keratosis patient-applied treatments.3-7

Adherence to ingenol mebutate in clinical trials was high at over 98 per cent9, and is possibly due to the short duration of treatment. Current patient-applied therapies have treatment durations from three weeks up to 90 days3-7, longer treatment can lead to levels of patient adherence as low as 37 per cent.8*

In a recent survey, over 70 per cent of patients indicated that they found Picato® “very easy to use”.19**

The gel has been developed as a new treatment for non-hyperkeratotic, non-hypertrophic 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 ingenol mebutate was determined in four multicentre, randomised, double-blind, vehicle-controlled phase III studies. Results:

  • Following three days’ treatment of the face or scalp with ingenol mebutate 150mcg/g there was an 83 per cent median reduction in the number of lesions compared to baseline, when measured at Day 57.9
  • Following two days’ treatment of the trunk or extremities with ingenol mebutate 500mcg/g, there was a 75 per cent median reduction in the number of lesions compared to baseline, when measured at Day 57.9

Patients are likely to develop local skin responses (LSRs) following treatment with all patient- applied therapies for actinic keratosis. With ingenol mebutate, LSRs may start within one day of treatment, are generally predictable in nature and typically resolve within two weeks for the face and scalp and within four weeks for trunk and extremities.13

The majority of adverse events reported in the studies were local skin responses (LSRs).9 The most frequently reported LSRs were redness and flaking/scaling.9

The most common treatment-related adverse events other than LSRs were application-site reactions of itchiness, irritation and pain.9

Patients with complete clearance of actinic keratosis lesions at Day 57, ingenol mebutate (150mcg/g and 500mcg/g) demonstrated there was a sustained 87 per cent reduction of actinic keratosis lesions compared to original baseline after a further 12 months’ follow up.20

The Scottish Medicines Consortium published their Picato® acceptance advice on 12 March 2013, and the NICE Evidence Summary was published on 19 March 2013.

About actinic keratoses

Actinic keratosis (AK), also known as ‛solar keratosis’, is a common sun-induced skin lesion2, that is often a red, scaly patch that is not always easy to see21 and may be pre-cancerous.22

Actinic keratosis can be found as a single lesion or patch, and can commonly affect an area of skin (known as ‛the field’)12 particularly on parts of the body that are regularly exposed to the sun, such as the face, bald scalp, neck, upper chest and back, back of the hands and forearms.23

Actinic keratoses are common pre-malignant lesions, affecting up to 23 per cent of the British population aged 60+.24, 25

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.1

Every year there are more new cases of skin cancer in the UK than breast and lung cancers combined.16

There are two different types of skin cancer, one is related to moles, melanomas26, and the other is not, non-melanoma skin cancer including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).2 Both types of skin cancer are linked to too much sun exposure and both can be dangerous for your health.27

Studies have shown that:

  • 65 per cent of SCCs arise from actinic keratosis lesions;28, 29
  • eight per cent of actinic keratoses progress to SCCs per year (estimated average);30
  • there is no way to predict which actinic keratoses will progress to SCCs;31
  • the risk of progression to SCC increases with the number of lesions present;32
  • people with actinic keratosis are approximately five times more likely to develop head or neck melanoma than those without.33

Source

* 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.

**Data from US Patient Experience Program survey (2012). Patients using Picato® to treat AK lesions on face or scalp filled in a questionnaire with eight multiple choice questions. Response rate to each question was over 93 per cent. 70.3 per cent figure based on 444 patient responses.

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

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

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

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

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

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

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

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

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

10. Stockfleth E et al. Eur J Dermatol. 2008; 18:651-59

11. Feldman SR and Fleischer AB, Jr. Cutis. 2011; 87:201-7

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

13. [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. [Last accessed March 2013]

14. Scottish Medicines Consortium, March 2013 ingenol mebutate, 150 & 500 micrograms/g, gel (Picato®). SMC No. (851/13). Available at http://www.scottishmedicines.org.uk.

15. NICE evidence summary – ESNM14: Actinic keratosis: ingenol mebutate gel. Available at http://publications.nice.org.uk/esnm14-actinic-keratosis-ingenol-mebutate-gel-esnm14.

16. 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]

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

18. Berman B. Clinical, Cosmetic and Investigational Dermatology. 2012; 5 111–22

19. 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.

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

21. 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]

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

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

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

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

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

27. 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]

28. Criscione VD et al. Cancer. 2009; 115:2523 – 30

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

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

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

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

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

LEO Pharma UK/IE