In February 2012 CLINUVEL submitted a marketing authorisation application for SCENESSE® (afamelanotide 16mg) for erythropoietic protoporphyria (EPP) with the European Medicines Agency. In December 2014, the European Commission approved SCENESSE® for the prevention of phototoxicity in adult EPP patients. For more information, please see the Company's announcement.
In June 2018 CLINUVEL submitted a new drug application with the US FDA seeking marketing authorisation for SCENESSE®. In January 2019 the FDA set a PDUFA date of 8 July 2019 and granted SCENESSE® a Priority Review.
Phase III results - Europe, the USA and Australia
CLINUVEL has completed three Phase III studies of SCENESSE® (afamelanotide 16mg) in patients with EPP.
In 2010 CLINUVEL completed its first Phase III study of SCENESSE® in patients with EPP (CUV017). A total of 91 patients completed the 12-month study, in which an 11-point Likert scale and physician assessments through case report forms (CRF) were used to evaluate pain as a principal symptom of phototoxicity. The duration of daily (sun)light exposure was used to assess the willingness of patients to expose themselves during all seasons. Melanin density (reflecting changes in skin pigmentation, measured by spectrophotometry) and quality of life (Short Form 36 surveys) were also evaluated.
In an analysis of the total number of days (frequency distribution) on which patients experienced pain in the specific pain severity categories (severe, moderate, mild and none), a significant reduction of frequency was observed in patients on active drug [p=0.0023]. Characteristic to EPP, the majority of phototoxic reactions occurred during spring and summer.
In analysing the average pain severity experienced by the total number of patients, the assessment of all individual daily pain scores was significantly lower in patients receiving SCENESSE® compared to those receiving placebo [p=0.0017].
An additional evaluation of the pain scores in patients willing to modify behaviour by continuous exposure to daily (sun)light showed a positive trend toward a reduction in average pain score following active drug treatment [p=0.1654]. You can view the full Phase III results from our CUV017 EPP study here.
In 2011, CLINUVEL completed a second Phase III study of SCENESSE® in patients with EPP (CUV029). Sixty-eight patients completed the nine month study across eight academic centres in Europe. Patients were evenly distributed between two treatment groups across all study sites, receiving either afamelanotide or placebo treatment every 60 days.
Results of the study showed that SCENESSE® was well tolerated, allowed EPP patients to expose their skin to sunlight during the middle of the day without or with reduced pain and improved their Quality of Life (QoL). Overall the study demonstrated a strong clinical benefit to patients, despite their deeply learned behaviour to avoid reactions caused by sun exposure.
View the full Phase III results from our CUV029 study here.
A confirmatory US Phase III study study of SCENESSE® (afamelanotide 16mg) in EPP patients was completed in 2013. CUV039 was a six-month, randomised, multicentre, double-blind, placebo-controlled Phase III study which recruited 93 adult EPP patients in the seven main US porphyria specialist centres (Alabama, California, Michigan, New York, North Carolina, Texas and Utah). Patients were randomised into two treatment groups and given either SCENESSE® or placebo implants every two months (at days 0, 60 and 120). A final visit for safety follow-up was scheduled on day 210. Of the 93 patients enrolled, 87 completed the study (93.5%), 45 on active treatment and 42 placebo recipients. Three from each group withdrew from the study due to reasons unrelated to drug administration.
The primary endpoint was to establish the extent to which patients exposed themselves to direct sunlight between 10:00 and 18:00 as recorded daily in patient diaries. A strong trend towards greater direct sunlight exposure was seen in the active group compared to placebo recipients. Median total direct sunlight exposure was 64.13 hours (range 0 - 650.5 hours) in the active group compared with 47.5 hours (range 0 - 224 hours) for placebo recipients (p=0.107, Kruskal-Wallis test). The distribution of the number of days with sun exposure of various time intervals (30 min intervals) was significantly different between the treatment groups (p0.001, Cochran-Mantel-Haenszel test). As an example, SCENESSE® recipients reported more days when they had pain-free exposure of 60 minutes or more (the time of greatest risk of burns).
To provide an objective measure of light tolerance in support of the primary endpoint, photoprovocation under standardised laboratory conditions was performed in 20 patients at Mount Sinai Hospital. The results showed that after receiving their second SCENESSE® administration, patients had a significantly higher tolerance to light irradiation on the lower back and back of the hand (median change from baseline in minimum symptom dose on lower back at day 90, 227.5 versus -2.4 J/cm2; p0.001, Wilcoxon test). Results for the lower back at day 120 and the back of the hand at days 90 and 120 showed similar significant differences.
As a secondary endpoint, QoL was evaluated using the validated EPP-QoL questionnaire. Active drug recipients showed significantly improved QoL scores in comparison to placebo recipients on days 60, 120 and 180 of the study (p=0.002, 0.002 and 0.004 respectively, Kruskal-Wallis test).
A further secondary endpoint looked at the distribution of days on which patients experienced mild, moderate or severe phototoxic pain. The difference in the distribution of days during which pain was experienced was significant between the two treatment groups (p0.0001, Cochran-Mantel-Haenszel test).
You can read the full results from the CUV039 study here.
Phase II results - the USA
In 2011 CLINUVEL completed a Phase II study (CUV030) SCENESSE® in adult US EPP patients. This six-month, randomised, multicentre, double-blind, placebo-controlled US study (CUV030) was primarily designed to confirm the efficacy and safety of subcutaneous bioresorbable afamelanotide implants (SCENESSE®) in reducing the severity of phototoxic skin reactions in patients with the rare light intolerance disorder erythropoietic protoporphyria (EPP), allowing them to lead ‘more normal’ lives.
Results of the study showed that SCENESSE® was well tolerated, allowed EPP patients to expose their skin to sunlight during the middle of the day and improved their Quality of Life (QoL). Read the company's Phase II US EPP results announcement.
Phase II results - Europe
In 2007 CLINUVEL completed a Pilot Phase II study (CUV010) of SCENESSE® assessing the drug’s ability to reduce the number and severity of phototoxic reactions. In all five patients, the time to provoke pain (photoprovocation) was markedly prolonged (range: 384% - 1266%). Read the company’s Phase II EPP results announcement.