December Horizon Scanning Research & 2016 Intelligence Centre Afamelanotide 16mg Implant (SCENESSE) for generalised vitiligo – first line in combination with narrow-band ultraviolet B light (NB-UVB) NIHR HSRIC ID: 6667 Lay summary Afamelanotide is a new drug to treat generalised vitiligo. Vitiligo is a long-term condition where white patches develop on the skin, because of a lack of pigment in the skin. This condition may cause significant psychological distress. Afamelanotide is administered as an implant once every 28 days with NB-UVB light therapy administered 2-3 times per week. If licensed, afamelanotide may offer an additional treatment option for patients with this condition. This briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. Horizon Scanning Research & Intelligence Centre University of Birmingham [email protected] www.hsric.nihr.ac.uk @OfficialNHSC TARGET GROUP • Generalised vitiligo: adults; stable or slowly progressing; with 10-50% of total body surface involvement – first line; in combination with narrow-band ultraviolet B light (NB- UVB). TECHNOLOGY DESCRIPTION Afamelanotide (SCENESSE; [Nle4,D-Phe7]-alpha-MSH; CUV-1647; EPT-1647; melanotan I; melanotan) is a structural analogue of endogenous alpha-melanocyte-stimulating hormone (α-MSH), which is formulated as a bioresorbable implant. Afamelanotide acts as an agonist at the melanocortin 1 receptor, activating the synthesis and transport of eumelanin. Afamelanotide may facilitate repigmentation and proliferation of melanocytes from melanocyte reservoirs and is also believed to have antioxidant and immunomodulatory properties. In a phase II clinical trial, afamelanotide 16mg implant was administered subcutaneously (SC) once every 28 days for a total of 6 implants in combination with NB-UVB light administered 3 times per week, for a total of 72 treatments1. Afamelanotide implant (as SCENESSE) has Marketing Authorisation in the EU for the prevention of phototoxicity in adult patients with erythropoietic protoporphyria2. The most common adverse events with SCENESSE are nausea, headache, and mild reactions at the implant site, such as discoloration, pain and redness, which affects around 1 in 5 patients. SCENESSE must not be used in patients with reduced liver or kidney functions2. INNOVATION and/or ADVANTAGES If licensed, afamelanotide may offer an additional treatment option for patients with generalised vitiligo. DEVELOPER Clinuvel Pharmaceuticals Ltd. AVAILABILITY, LAUNCH OR MARKETING In phase II clinical trials. PATIENT GROUP BACKGROUND Vitiligo is an acquired, chronic depigmentation disorder that manifests as white macules on the skin, which increase in size over time, and may cause significant psychological stress3. Vitiligo is classified into segmental vitiligo and vitiligo (referred to in the past as nonsegmental vitiligo), which includes the most common form of the condition, generalised vitiligo, that accounts for 85-90% of people with this condition4. Vitiligo can affect any area of Horizon Scanning Research & Intelligence Centre the skin, but most commonly occurs on the face, neck, extremities and in the skin creases5. Generalised vitiligo presents with a widespread distribution of macules, and is usually symmetrical4. Depigmentation mainly occurs due to the loss of functioning melanocytes in the skin. The cause is not clearly understood, but the aetiology includes genetic, environmental, autoimmune, and viral factors6,5. CLINICAL NEED and BURDEN OF DISEASE Vitiligo indiscriminately affects 1-2% of the general population, and is more commonly diagnosed in women and people with darker skin pigmentation4. In the UK, about 1 in 100 people develop vitiligo, and while around half of people are affected before the age of 20, it can occur at any age3,5. Vitiligo is a disease that significantly impairs quality of life, but the degree of impact at the population level depends to some extent on the ethnic make-up of the population7. In Western Europe, the proportion of people who have diagnosable psychiatric morbidity associated with the condition is estimated to be between 25-30%; however in India, the proportion of people with vitiligo and an associated psychiatric morbidity is estimated to be between 56-75%8. The population likely to be eligible to receive afamelanotide could not be estimated from available published sources. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE medical technology guidance. The ReCell spray-on skin system for treating skin loss, scarring and depigmentation after burn injury (MTG21). November 2014. NHS England Policies and Guidance • NHS England. 2013/14 NHS Standard Contract for Specialised Dermatology Services (All Ages). A12/S/a. Other Guidance • Primary Care Dermatology Society. Vitiligo. 20169. • NICE Clinical Knowledge Summary. Vitiligo. 20164. • European Dermatology Forum. Guidelines for Vitiligo. 20148. • British Association of Dermatologists. Guidelines for the management and diagnosis of vitiligo. 200810. CURRENT TREATMENT OPTIONS Currently there is no cure for vitiligo and no effective treatments that promote repigmentation and/or halt its progression with lasting effects3.Therapies currently used in adults include:3,4,8,9 • Topical treatment – potent or highly potent corticosteroids, vitamin D analogues, and calcineurin inhibitors (e.g. pimecrolimus or tacrolimus, used mainly for the face and neck area as an alternative to topical steroids). These should be taken for a period no longer than 3 months. 3 Horizon Scanning Research & Intelligence Centre • Phototherapy – NB-UVB phototherapy for adults whose disease cannot be managed with topical treatments, have widespread vitiligo, or have localised vitiligo associated with a significant impact on their quality of life. NB-UVB should be used in preference to oral psoralen combined with ultraviolet A light (PUVA). However, no consensus exists as to the optimum duration of phototherapy, and practice varies widely. • Psychological support and counselling. • Surgical treatments for sites where there have been no new lesions, no extension of the lesion in the past year, and no Koebner phenomenon. Treatment results vary between individuals4. NB-UVB phototherapy is the most effective treatment for patients with moderate to severe condition, however none are optimal and more therapeutic interventions for vitiligo are needed10. EFFICACY and SAFETY Trial NCT01382589, CUV101, NCT01430195, CUV102; CUV103; afamelanotide or EudraCT:2011-000169-10; afamelanotide and NB- placebo, both with NB-UVB afamelanotide with NB- UVB light therapy vs NB- light therapy; phase II. UVB light therapy vs NB- UVB light therapy only; UVB light therapy only; phase II. phase II. Sponsor Clinuvel Pharmaceuticals Clinuvel Pharmaceuticals Clinuvel Pharmaceuticals Status Completed. Completed. Ongoing. Source of Trial registry1. Publication11, trial Press release13. information registry12, and manufacturer. Location France, Italy and USA. Singapore. Switzerland. Design Randomised, active- Randomised, active- Randomised, placebo- controlled. controlled. controlled. Participants n=15; aged ≥18 yrs; n=56; aged ≥18 yrs; n=21 (planned); aged ≥21 confirmed diagnosis of confirmed diagnosis of yrs; Fitzpatrick skin types III generalised vitiligo with 15- generalised vitiligo with and VI; confirmed diagnosis 50% of total body surface 15-50% of total body generalised vitiligo with 15- involvement; stable or surface involvement; 50% of total body surface slowly progressive vitiligo stable or slowly involvement; stable or over a 3-month period; progressive vitiligo over a slowly progressive vitiligo Fitzpatrick skin types III-VI; 3-month period; over a 3-month period; no vitiligo involving the Fitzpatrick skin types III- vitiligo involving head and hands and feet only; no VI; no vitiligo involving the neck; no vitiligo involving extensive leukotrichia; no hands and feet only; no the hands and feet only; no vitiligo of ≥5 yrs duration; extensive leukotrichia; no extensive leukotrichia; no no treatment with NB-UVB vitiligo of ≥5 yrs duration; treatment with NB-UVB within 6 mths; no allergy to no treatment with NB- within 6 weeks; no allergy afamelanotide, the polymer UVB within 6 mths; no to afamelanotide, or contained in the implant, or allergy to afamelanotide, lignocaine/lidocaine or lignocaine or lignocaine/lidocaine or other local anaesthetic /lidocaine or other local other local anaesthetic used during administration; anaesthetic used during used during no treatment with topical administration; no administration; no immunomodulators treatment with topical treatment with topical (corticosteroids, calcineurin immunomodulators immunomodulators inhibitors) within 4 wks. (corticosteroids, calcineurin (corticosteroids, inhibitors) within 4 wks. calcineurin inhibitors) within 4 wks. 4 Horizon Scanning Research & Intelligence Centre Schedule Randomised to Randomised to Randomised to afamelanotide16mg implant afamelanotide 16mg afamelanotide 16mg administered (SC) once implant administered SC implant administered SC every