Phase IIa proof of concept study of SCENESSE® in variegate porphyria
Clinical and regulatory progress:
In October 2018, CLINUVEL announced that it has reached agreement with two European porphyria expert centres on a clinical trial protocol to conduct a Phase IIa proof of concept study evaluating the safety and efficacy of SCENESSE® (afamelanotide 16mg) in variegate porphyria (VP).
The study (CUV040) will start patient treatment in the northern hemisphere spring of 2019.
About variegate porphyria
The porphyrias are a group of nine genetic metabolic diseases, including VP and EPP, characterised by specific enzyme deficiencies along the biochemical pathway of haem synthesis.
VP is a rare autosomal dominant inherited disorder resulting from the deficiency of the mitochondrial enzyme protoporphyrinogen oxidase (PPOX), the sixth enzyme of the haem biosynthesis pathway.
A debilitating and burdensome disease for patients, VP is classified as both a cutaneous and acute porphyria. The cutaneous symptoms are characterised by adult-onset blistering lesions (bullous symptoms, subepidermal vesicles) and chronic fragility (hypotrophy and hypoplasia) of sun and light-exposed skin, especially the back of the hands and the face. The propensity of the dermis to form wounds (lesions and erosions which form crusts, heal slowly or not at all, and are prone to infection) following the mechanical use of hands and feet further restricts VP patients in their daily activities. Typically, patients experience scarring of the face, hands and feet. Patients diagnosed with VP experience phototoxicity and suffer episodes in spring and summer when the atmospheric intensity of light increases. The acute neurovisceral symptoms may present as severe episodes as early as adolescence, with women more affected than men. Psychiatric disturbances, autonomic neuropathy and muscle weakness have been reported in some patients.
The reported prevalence of VP varies from 0.3 to 2 cases per 100,000 inhabitants but has been reported as more common in the Caucasian South African population (up to 1 in 300 people) due to a founder effect.¹ European prevalence varies from 0.32 to 1 cases per 100,000 inhabitants, whereas the reported prevalence in the US is 0.5 cases per 100,000 inhabitants.
Currently, there is no standard of care or alternative therapy for cutaneous VP symptoms. Patients are forced to lead a life sheltered from light and to avoid any mechanical contact with their skin surface or risk of triggering wounds and long-lasting blistering.
¹ Elder et al (2012). The incidence of inherited porphyrias in Europe. J Inherit Metab Dis.
Horner et al (2013). Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology.
In J Dermatol. Singal & Anderson (2013). Variegate Porphyria. GeneReviews®. Online at: https://www.ncbi.nlm.nih.gov/books/NBK121283/