ScenesseErythropoietic protoporphyria - prevention of phototoxicity in adults
New molecular entity
Development and Regulatory status
Licensed but not launched
Jun 20NICE is planning a virtual stakeholder engagement workshop for this topic. The date of the workshop along with further timelines are TBC .
Apr 20Launched in US .
Jan 20No update available on NICE website regarding the HST; assume UK launch is delayed pending action following the appeal .
Oct 19Approved in the US 
Oct 18NICE appeal panel upholds the appeal on several grounds. The evaluation committee must now address a number of issues including consideration of the trial results .
Jul 18Appeal panel convened to consider an appeal against NICE ’s FAD on afamelanotide for treating EPP .
Apr 17Clinuvel reaches an agreement with the German National Association of Statutory Health Insurance Funds (GKV-SV) regarding the German pricing of afamelanotide for treatment of EPP .
May 16Clinuvel announce that the process of regulatory drug release and approval of the pharmacovigilance systems required a further 18 months of in-depth discussion with the EMA. The EMA’s pharmacovigilance subcommittee (PRAC) formally endorsed the last of these protocols on April 14, 2016. The final regulatory and clinical steps prior to the start of the treatment are a review of the PASS and RCR protocols by some of the local ethics committees and the approval of patient and physician educational materials by various National Competent Authorities. SCENESSE® is only being made available to EPP patients through Porphyria Expert Centres, which require training and accreditation by Clinuvel. In Germany it is anticipated that the first year three Porphyria Expert Centres – in Berlin, Chemnitz, and Düsseldorf – will be able to prescribe the treatment. The German national authorities have released their first assessment of the use of SCENESSE® in EPP. In parallel, 13 German insurance firms have agreed to make SCENESSE® available to EPP patients. It is the company’s expectation for a uniform commercial price to be in place across Europe. Discussions are underway with authorities in nine countries to make SCENESSE® available, with further submissions anticipated in 2016 
Feb 15Approved in the EU
Oct 14EU positive opinion for afamelanotide to be used for prevention of phototoxicity in adults with EPP
Mar 14EMA review period extended to June 2014.
Feb 12Filed in the EU for prophylactic treatment in adult patients with EPP
Melanocyte stimulating hormone stimulant
EPP is a porphyria that affects at least 1 in 140,000 people in the UK. Protoporphyrin accumulates in the skin and causes severe photosensitivity: burning, excruciating pain and erythema, lasting 2-3 days and unresponsive to non-opiates.
Erythropoietic protoporphyria - prevention of phototoxicity in adults
Trial or other data
May 18NICE issues a final appraisal determination, not recommending afamelanotide for EPP because it is not cost-effective. The committee also considered that a managed access agreement would not have the plausible potential to reduce the uncertainties identified during the evaluation or to reduce the financial risk to the NHS .
Dec 17In draft guidance, NICE does not recommend afamelanotide. Final recommendation is expected May 20 .
Oct 15There are no other specific EPP treatments. Options include staying indoors, sun-blocking clothes and sunscreen. Likely to be expensive.
Jun 15Results of NCT01605136 and NCT00979745 published in NEJM. Patients in both the EU and USA arm were randomly assigned to receive a subcutaneous implant containing afamelanotide 16mg or placebo every 60 days. In the US study, duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04). In the European Union study, the duration of pain-free time after 9 months was also longer in the afamelanotide group than in the placebo group (median, 6.0 hours vs. 0.8 hours; P=0.005), and the number of phototoxic reactions was lower in the the afamelanotide group (77 vs. 146, P=0.04). In both trials, quality of life improved with afamelanotide therapy. Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug .
Mar 13Clinuvel plan to submit a Paediatric Investigational Plan (PIP) in the EU .
May 12NCT01605136 is a PIII placebo-controlled 6 month RCT enrolling between 75 and 100 eligible patients who will receive afamelanotide (16mg implants) or placebo on days 0, 60 and 120. The number and severity of phototoxic reactions, the type and duration of sun exposure, treatment-emergent adverse events and the use of concomitant medication will be recorded by patients in study diaries between Days 0 and 180. Quality of life will be measured using the DLQI and EPP-QoL. A subset of patients will be photoprovoked on the lower back and dorsal surface of the hand and the minimal symptom dose (MSD) will be determined on Days 0, 30, 60, 90 and 120. The study is planned to start Jun 12 and to complete Apr 13 .
Dec 11Results reported from the PIII CUV029 European study in 74 patients. 68 patients (91.9%) completed the study and 17,377 days were evaluated. Patients on afamelanotide (given as an implant every 60 days) had half as many phototoxic reactions as those on placebo (p=0.044), had a lower total median pain score (6.0 v 17.5; p=0.035) and total lower maximum pain score per phototoxic episode (4.0 v 6.0; p=0.018). Patient kept diaries showed that the patients in the afamelanotide group were able to spend more time in direct sunlight during periods of highest light and UV intensity (p=0.005). For the majority of study days, patients in the afamelanotide group were able to spend up to seven times longer in direct sunlight without experiencing pain. Afamelanotide patients could spent more time in direct sunlight on days when they reported no pain (10 AM-3 PM, p=0.005; 10 AM-8 PM, p=0.003) and on days when they reported no pain or mild pain (10 AM-3 PM, p=0.032; 10 AM-8 PM, p=0.012). Using a a specialised EPP-specific QoL questionnaire (EPP-QoL), patients on afamelanotide reported greater improvement in their QoL and the difference was significant on Days 120 (p=0.005) and 270 (p=0.011). Most common AEs were associated with implant administration (pain or bruising following injection), transient nausea, headache and the common cold .
Nov 11Results of the 6-month US double blind, PII RCT (CUV030) reported. 77 patients were randomized to afamelanotide implant or placebo at study start, after 60 days and 120 days, and were followed up to 180 days. Based on diary records, afamelanotide increased patients´ ability to expose their skin to direct sunlight, based on time spent outside. Patients on afamelanotide spent significantly more time in direct sunlight between the most intense hours of 10 AM and 3 PM (p=0.036) and between 10 AM and 8 PM (p=0.025). They reported a 3-fold increase in the median amount of time in direct sunlight vs placebo and many reported no pain or only mild pain compared to their previous life of experiencing severe phototoxic reactions. Data from an EPP-specific QoL assessment tool showed an improvement from baseline for patients on afamelanotide vs placebo at 60 days (p=0.001), 120 days (p=0.003) and 180 days (p<0.001). The drug appeared to be safe and well-tolerated .
Jul 10A 12 month European and Australian PIII study has reported that afamelanotide significantly reduced average daily pain severity scores vs placebo and allowed patients to expose their skin to sunlight and spend more time outdoors. It was well tolerated with no serious safety issues identified. Complete results will be presented at the 19th Congress of the European Association for Dermatology and Venereology in October .
May 10Afamelanotide could become the first-line treatment for EPP .
Dec 09Phase III, multicentre, randomised, double-blind, placebo-controlled trial (CUV 017) results announced for afamelanotide in erythropoietic protoporphyria (EPP) - interim analysis of data from the first 4 out of 12 months of treatment. The study used a crossover comparison of afamelanotide (3 doses) and placebo (3 doses) in 100 patients. At dose intervals of 2 months, each patient received a single dose of either treatment. Analysis of 2 treatment arms demonstrated an overall reduction in the average number of phototoxic reactions. 35 patients with severe and/or moderate pain reported the greatest reduction in mean number of reactions (95% CI). Analysis of pain severity was positively correlated with treatment, indicating that patient pain scores differed significantly between treatment groups (95% CI). Interim quality of life data reported a dramatic improvement in the pts ability to engage in outdoors activities. This study will be concluded by the end of December 2009 .
Aug 09Clinuvel expects to complete its first EU and Australian PIII trial (CUV017) in erythropoietic protoporphyria (EPP) by Q4 2009. Pending results, the company will file in Europe shortly after. The study started in Jun 07 and was expected to enrol 50-70 patients. Positive interim results - the reduction of the number and severity of phototoxic skin reaction - were reported in Jan 09. The company has now received European regulatory approval to begin a confirmatory multicentre 6 month PIII study (CUV029). The trial will be conducted in 5 centres in EU and will involve around 40 patients. Afamelanotide is delivered through a biodegradeable, subcutaneous, controlled-release implant [1,2].