Afamelanotide

SCENESSE ® is indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP). SCENESSE is a melanocortin 1 receptor (MC1-R) agonist indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP)

Implant: 16 mg of afamelanotide as a solid white to off-white, bioresorbable, sterile rod approximately 1.7 cm in length and 1.45 mm in diameter. Implant: 16 mg of afamelanotide .

SCENESSE is contraindicated in patients with a history of severe hypersensitivity reaction to afamelanotide or to any of the excipients in SCENESSE . Known hypersensitivity to afamelanotide or to any of the excipients in SCENESSE .

Hypersensitivity Skin Monitoring Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of SCENESSE. Warn patients of the risk of hypersensitivity reactions, including anaphylaxis. If a serious hypersensitivity reaction occurs, initiate appropriate therapy and remove the SCENESSE implant if needed [ see Dosage and Administration ]. The patient should not receive any further treatment with SCENESSE. [ see Contraindications ]. SCENESSE may lead to generalized increased skin pigmentation and darkening of pre-existing nevi and ephelides because of its pharmacologic effect. A full body skin examination (twice yearly) is recommended to monitor pre-existing and new skin pigmentary lesions. Hypersensitivity: Serious hypersensitivity reactions, including anaphylaxis, have been reported. If a serious hypersensitivity reaction occurs, initiate appropriate therapy and remove the SCENESSE implant if needed. The patient should not receive any further treatment with SCENESSE . Skin Monitoring: May induce darkening of pre-existing nevi and ephelides due to its pharmacological effect. A full body skin examination (twice yearly) is recommended to monitor pre-existing nevi and new skin pigmentary lesions .

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 16 mg 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). 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 reaction 1 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 hyperpigmentation 2 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. Specific Adverse Reactions Implant Site Reactions : Implant site reactions were more common in the SCENESSE group (21%) compared to the vehicle group (10%). In the SCENESSE group, the most common implant site reaction was implant site discoloration (10%). The most common adverse reactions (incidence > 2%) are implant site reaction, nausea, oropharyngeal pain, cough, fatigue, dizziness, skin hyperpigmentation, somnolence, melanocytic nevus, respiratory tract infection, non-acute porphyria, and skin irritation . To report SUSPECTED ADVERSE REACTIONS, contact CLINUVEL INC. at 1-888-288-2031 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See PATIENT COUNSELING INFORMATION . Postmarketing Experience The following adverse reactions have been identified during post-approval use of SCENESSE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: hypersensitivity (urticaria, angioedema, and anaphylaxis) [ see Warnings and Precautions ].

Postmarketing Experience The following adverse reactions have been identified during post-approval use of SCENESSE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: hypersensitivity (urticaria, angioedema, and anaphylaxis) [ see Warnings and Precautions ].

Pregnancy Risk Summary There are no data on SCENESSE use in pregnant women to evaluate for any drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome. In animal reproductive and development toxicity studies, no adverse developmental effects were observed with afamelanotide administration during the period of organogenesis to pregnant rats at subcutaneous doses up to 12 times the maximum recommended human dose (MRHD) ( see Data ). 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. Data Animal Data In embryofetal development studies in Sprague Dawley and Lister Hooded rats, afamelanotide was administered subcutaneously to pregnant rats at doses of 0.2, 2, or 20 mg/kg/day throughout the period of organogenesis. No adverse embryofetal developmental effects were observed at doses up to 20 mg/kg/day (12 times the MRHD, based on a body surface area comparison). In a pre- and post-natal development study in Sprague Dawley rats, afamelanotide was administered subcutaneously at doses of 0.2, 2, or 20 mg/kg/day during the period of organogenesis through lactation. No treatment-related effects were observed at doses up to 20 mg/kg/day (12 times the MRHD, based on a body surface area comparison). 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. Pediatric Use The safety and effectiveness of SCENESSE have not been established in pediatric patients. Geriatric Use There were 10 subjects 65 years old and over in the clinical studies for EPP [ see Clinical Studies ]. 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 experience has not identified differences in responses between the elderly and younger patients.

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.

Pediatric Use The safety and effectiveness of SCENESSE have not been established in pediatric patients.

Geriatric Use There were 10 subjects 65 years old and over in the clinical studies for EPP [ see Clinical Studies ]. 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 experience has not identified differences in responses between the elderly and younger patients.