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 ].

<table border="0" width="100%"><caption>Table 1: Adverse Reactions Occurring in More Than 2% of Subjects with EPP Through Month 6 (Studies CUV039, CUV030, and CUV029)</caption><tbody><tr><td><content styleCode="bold">Adverse Reaction</content></td><td><content styleCode="bold">SCENESSE n (%) N = 125 </content></td><td><content styleCode="bold">Vehicle n (%) N = 119 </content></td></tr><tr><td>Implant site reaction ¹</td><td>26 (21%)</td><td>12 (10%)</td></tr><tr><td>Nausea</td><td>24 (19%)</td><td>17 (14%)</td></tr><tr><td>Oropharyngeal pain</td><td>9 (7%)</td><td>6 (5%)</td></tr><tr><td>Cough</td><td>8 (6%)</td><td>4 (3%)</td></tr><tr><td>Fatigue</td><td>7 (6%)</td><td>3 (3%)</td></tr><tr><td>Skin hyperpigmentation ²</td><td>5 (4%)</td><td>0 (0%)</td></tr><tr><td>Dizziness</td><td>5 (4%)</td><td>4 (3%)</td></tr><tr><td>Melanocytic nevus</td><td>5 (4%)</td><td>2 (2%)</td></tr><tr><td>Respiratory tract infection</td><td>5 (4%)</td><td>3 (3%)</td></tr><tr><td>Somnolence</td><td>3 (2%)</td><td>1 (1%)</td></tr><tr><td>Non-acute porphyria</td><td>2 (2%)</td><td>0 (0%)</td></tr><tr><td>Skin irritation</td><td>2 (2%)</td><td>0 (0%)</td></tr></tbody></table>