Afamelanotide for erythropoietic protoporphyria and congenital erythropoietic porphyria

Transcription

1 Afamelanotide for erythropoietic protoporphyria and congenital erythropoietic porphyria This technology summary 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. The Research Programme is part of the National Institute for Health Research

2 Afamelanotide for erythropoietic protoporphyria and congenital erythropoietic porphyria Target group Erythropoietic porphyrias: Erythropoietic protoporphyria (EPP). Congenital erythropoietic porphyria (CEP). Background The two porphyria disorders EPP and CEP, belong to a group of seven disorders that disrupt the haem biosynthesis pathway. Each disorder affects a different enzyme in the pathway, reducing the functional activity of the enzyme and leading to the accumulation of various haem precursors 1. Generally these disorders are inherited, but there have been some cases of acquired porphyria disorders reported 2. The exception to this is porphyria cutanea tarda (PCT) which is acquired by approximately 90% of cases. The disorders can be broadly classified into three groups according to the pattern of accumulation and excretion of the haem precursors: acute (neuropsychiatric), cutaneous and mixed. This pattern along with the identification of the particular haem biosynthesis enzyme affected is used to diagnose and distinguish between the disorders. However, the clinical features are not specific to any one disorder 1. Both EPP and CEP are classified as cutaneous porpyhria disorders. Erthropoietic protoporphyria Haem biosynthesis deficient enzyme: ferrochelatase. Haem precursor increased: protoporphyrin IX (PpIX). Haem precursor accumulation in: erythrocytes, plasma, liver and skin. Clinical features: Appears in childhood, rarely after eight years of age. The main clinical feature is severe photosensitivity leading to burning, pain, pruritis and erythema within a few minutes of sun exposure (particularly in the spring and summer months) which lasts 2-3 days, leads to loss of sleep and is unresponsive to non-opiate analgesics. In a small number of patients (1-4%) accumulation of PpIX in the liver leads to liver failure; gallstones can also occur in some patients. A large study of UK patients with EPP found: o o 70% of the adults scored >10 on the Dermatological Life Quality Index (DLQI). 80% of the children scored >10 on the Children s Dermatological Life Quality Index (CDLQI) 3. Congenital erythropoietic porphyria Haem biosynthesis deficient enzyme: uroporphyrinogen-iii. Haem precursors increased: uroporphyrinogen, coprophyrinogen and protoporphyrin. Haem precursor accumulation in: erythrocytes, liver, skin, bones, teeth (producing a red to brown discolouration). Clinical features: Severe photosensitivity of skin leading to pruritus and erythema. Vesiculobullous lesions form on exposed skin and can become infected. Healing of lesions leads to hyperpigmentation, hypertrichosis, scarring and disfigurement from cartilage and bone reabsorption especially of the hands and nose. Severe scarring around the mouth can limit the capacity to open the mouth. Other clinical features include functional loss in the hands, loss of vision from keratoconjunctivitis, and haemolytic anaemia, which can lead to fragile long bones and vertebrae. In many cases death occurs in early adulthood from complications associated with severe haemolytic anaemia. 2

3 Technology description Afamelanotide (CUV1647) is a synthetic analogue of alpha melanocytes stimulating hormone (α-msh) and acts as an agonist of the melanocortin-1-receptor (MC1R), activating melanogenesis. Afamelanotide is a photoprotective agent because it induces the synthesis of melanin pigmentation in the skin. Afamelanotide is administered using a bioresorbable implant inserted subcutaneously. Each implant contains a 16mg dose with new implants required every 60 days. Afamelanotide is in phase III clinical trials for polymorphic light eruption (PLE). Innovation and/or advantages Afamelanotide represents a new class of drug and would be the first specifically licensed product for these patient groups. Developer Clinuvel Pharmaceuticals Limited. Availability, launch or marketing dates, and licensing plans: In phase III clinical trials. NHS or Government priority area This topic relates to the National Service Framework for Children, Young People and Maternity Services: The mental health and psychological well being of children and young people. (2004) and National Service Frameworks for Children, Young People and Maternity Services: Medicines for children and young people. (2004). Clinical need and burden of disease A survey in 2006 of five referral centres across the UK identified 389 patients with EPP 3. Of this group 223 patients volunteered to take part in a study of EPP impact on patients with 20% aged between 6-16 years of age. CEP is one of the rarest porphyria disorders with a prevalence in the UK of less than 1 per million. Existing comparators and treatments At this time there are no specific pharmacological treatments for EPP or CEP. Nonpharmacological options include sunlight avoidance strategies e.g. staying indoors or seeking shade during sunny periods, wearing sunlight blocking clothing and sunscreen. In severe cases of EPP the patient has to remain indoors during the spring and summer months or they will face frequent cutaneous debilitating attacks. Patients with CEP and haemolytic anaemia will require recurrent transfusions, and some have been treated using allogenic bone marrow transplants 2. Efficacy and safety Trial Sponsor Status Location Design Participants and schedule ACTRN : Erythropoietic protoporphyria; phase III. Clinuvel Pharmaceuticals Limited. Ongoing. Australia, EU. Randomised; placebo controlled. n=101; 18 or older. Randomised to 16mg CUV1647 or placebo, implanted every 60 days for 12 months. 3

4 Follow-up Primary outcome Secondary outcome Expected reporting date Adverse effects 12 months. Phototoxic reactions. Duration of sunlight tolerance; melanin density and quality of life (QoL). Q Estimated cost and cost impact The cost of afamelanotide implant is not yet known. Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Services Increased use: implantation and reimplantation Reduced mortality or increased length of survival Other: Service reorganisation required Improved quality of life for patients and/or carers None identified Staff or training required Decreased use Other: None identified Costs Increased unit cost compared to alternative Increased costs: more patients coming for treatment Increased costs: capital investment needed New costs Savings: Other: References 1 Thadani H, Deacon A and Peters T. Diagnosis and management of porphyria. British Medical Journal. 2009; 320: Gross U, Horrman G F and Doss M O. Erthropoietic and hepatic porphyrias. Journal of Inherited Metabolic Disease. 2000; 23: Holme S A, Anstey A V, Finlay A Y et al. Erythropoietic protoporphyria in the UK: Clinical features and effect on quality of life. British Journal of Dermatology 2006; 155: World Health Organisation clinical trials registry. A phase III, multicentre, randomised, placebo-controlled study to evaluate the safety and efficacy of subcutaneous bioresorbable CUV1647 implants in patients with Erythropoietic Protoporphyria (EPP) Accessed 25 th November. 4

5 The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)