Warnings and Precautions
Skin monitoring: May lead to generalized increase in skin pigmentation and darkening of pre-existing nevi and ephelides due to its pharmacological effect. A regular full body skin examination (twice yearly) is recommended to monitor pre-existing and new skin pigmentary lesions.
The most common adverse reactions (incidence > 2%) include implant site reaction, nausea, oropharyngeal pain, cough, fatigue, dizziness, skin hyperpigmentation, somnolence, melanocytic nevus, respiratory tract infection, non-acute porphyria, and skin irritation.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of SCENESSE® was evaluated in 3 randomized, multicenter, prospective, vehicle controlled clinical trials (Study CUV029, Study CUV030, and Study CUV039) involving 244 adult subjects with Erythropoietic Protoporphyria (EPP) without significant liver involvement. Subjects received subcutaneous SCENESSE® implants containing 16mg of afamelanotide every 2 months. A total of 125 subjects received SCENESSE® and 119 subjects received vehicle implants.
Table 1 summarizes the adverse reactions that occurred in more than 2% of subjects.
Table 1: Adverse Reactions Occurring in More Than 2% of Subjects with EPP Through Month 6 (Studies CUV039, CUV030, and CUV029)
|Adverse Reaction||SCENESSE n (%) N = 125||Vehicle n (%) N = 119|
|Implant site reaction¹||26 (21%)||12 (10%)|
|Nausea||24 (19%)||17 (14%)|
|Oropharyngeal pain||9 (7%)||6 (5%)|
|Cough||8 (6%)||4 (3%)|
|Fatigue||7 (6%)||3 (3%)|
|Skin hyperpigmentation²||5 (4%)||0 (0%)|
|Dizziness||5 (4%)||4 (3%)|
|Melanocytic nevus||5 (4%)||2 (2%)|
|Respiratory tract infection||5 (4%)||3 (3%)|
|Somnolence||3 (2%)||1 (1%)|
|Non-acute porphyria||2 (2%)||0 (0%)|
|Skin irritation||2 (2%)||0 (0%)|
¹: Implant site reaction includes: implant site bruising, discoloration, erythema, hemorrhage, hypertrophy, irritation, nodule, pain, pruritus, swelling; injection site bruising and erythema; and expelled implant.
²: Skin hyperpigmentation includes skin hyperpigmentation, pigmentation lip (subject also had skin hyperpigmentation), and pigmentation disorder.
Use in Specific Populations
Pregnancy Risk Summary
There are no data on SCENESSE® use in pregnant women to evaluate any drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Lactation Risk Summary
There are no data on the presence of afamelanotide or any of its metabolites in human or animal milk, the effects on the breastfed infant, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SCENESSE® and any potential adverse effects on the breastfed infant from SCENESSE® or from the underlying maternal condition.
The safety and effectiveness of SCENESSE® have not been established in pediatric patients.
There were 10 subjects 65 years old and over in the clinical studies for EPP [see Clinical Studies (14)]. Of the 125 subjects treated with SCENESSE® in these studies, 4 (3%) were 65 years of age and older. Clinical studies of SCENESSE® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experiences have not identified differences in responses between elderly and younger patients.
Three vehicle-controlled, parallel-group clinical trials of SCENESSE® were conducted in subjects with EPP. Of these trials, two (Study CUV039, NCT 01605136, and Study CUV029, NCT 00979745) were designed to assess exposure to direct sunlight on days with no phototoxic pain. The two trials differed in the number of days of follow-up, the time windows within a day in which time spent outdoors was recorded, and how the amount of time spent in direct sunlight on each day was characterized. The subjects enrolled in these trials were primarily Caucasian (98%), the mean age was 40 years (range 18 to 74 years), and 53% of subjects were male and 47% were female.