SCENESSE® is indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP).

SCENESSE should be administered by a health care professional. All healthcare professionals should be proficient in the subcutaneous implantation procedure and have completed the training program provided by CLINUVEL prior to administration of the SCENESSE implant [ see Dosage and Administration]. Additional information, including a video, is available at http://www.clinuvel.com/US-HCP. The additional information has not been evaluated or approved by the FDA.

A single SCENESSE implant is inserted subcutaneously above the anterior supra-iliac crest every 2 months.

Use the SFM Implantation Cannula to implant SCENESSE. Contact CLINUVEL INC. for other implantation devices that have been determined by the manufacturer to be suitable for implantation of SCENESSE.

Maintain sun and light protection measures during treatment with SCENESSE to prevent phototoxic reactions related to 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.

None.

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.

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).

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%).

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).

SCENESSE (afamelanotide) implant is a controlled-release dosage form for subcutaneous administration. Afamelanotide is a melanocortin 1 receptor (MC1-R) agonist. The active ingredient afamelanotide acetate is a synthetic peptide containing 13 amino acids with molecular formula C 78H 111N 21O 19 •xC 2H 4O 2 (3 ≤ x ≤ 4). The molecular weight of afamelanotide is 1646.85 (anhydrous free base). Afamelanotide acetate has the following structure:

Ac-Ser-Tyr-Ser-Nle-Glu-His-(D)Phe-Arg-Trp-Gly-Lys-Pro-Val-NH 2• xCH 3COOH.

Afamelanotide is a white to off-white powder, freely soluble in water. Each SCENESSE implant contains 16 mg of afamelanotide (equivalent to 18 mg of afamelanotide acetate), and 15.3-19.5 mg of poly (DL-lactide-co-glycolide).
SCENESSE implant is a single, solid white to off-white, bioresorbable and sterile rod approximately 1.7 cm in length and 1.45 mm in diameter. The implant core comprises of the drug substance admixed with a poly (DL-lactide-co-glycolide) bioresorbable copolymer.

Afamelanotide is a synthetic tridecapeptide and a structural analog of α-melanocyte stimulating hormone (α-MSH).
Afamelanotide is a melanocortin receptor agonist and binds predominantly to MC1-R.

Carcinogenicity studies have not been conducted with SCENESSE.

Afamelanotide was negative in the Ames test, in vitro mouse lymphoma assay, and in vivo mouse bone marrow micronucleus assay.

No effects on male or female fertility and reproductive performance were observed in rats at subcutaneous doses up to 20 mg/kg/day afamelanotide (12 times the MRHD, based on a body surface area comparison).

Three vehicle-controlled, parallel-group clinical trials of SCENESSE were conducted in subjects with EPP. Of these trials, two trials (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.

Study CUV039 enrolled 93 subjects, of whom 48 received SCENESSE (16 mg of afamelanotide administered subcutaneously every 2 months), 45 received vehicle. Subjects received three implants and were followed for 180 days. On each study day, subjects recorded the number of hours spent in direct sunlight between 10 am and 6 pm, the number of hours spent in shade between 10 am and 6 pm, and whether they experienced any phototoxic pain that day. The primary endpoint was the total number of hours over 180 days spent in direct sunlight between 10 am and 6 pm on days with no pain. The median total number of hours over 180 days spent in direct sunlight between 10 am and 6 pm on days with no pain was 64.1 hours for subjects receiving SCENESSE and 40.5 hours for subjects receiving vehicle.

Study CUV029 enrolled 74 subjects, of whom 38 received SCENESSE (16 mg of afamelanotide administered subcutaneously every 2 months), 36 received vehicle. Subjects received five implants and were followed for 270 days. On each study day, subjects recorded the number of hours spent outdoors between 10 am and 3 pm, whether “most of the day” was spent in direct sunlight, shade, or a combination of both, and whether they experienced any phototoxic pain that day.
The primary endpoint was the total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight. This analysis does not include sun exposure on days for which subjects reported spending time in a combination of both direct sunlight and shade. The median total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight was 6.0 hours for subjects in the SCENESSE group and 0.75 hours for subjects in the vehicle group.

SCENESSE (afamelanotide) implant, 16 mg, for subcutaneous administration (NDC 73372-0116-1) is supplied in a Type I amber glass vial sealed with a PTFE coated rubber stopper. Each vial contains one afamelanotide implant and is packaged individually in a cardboard box. SCENESSE implant is a solid white to off-white, bioresorbable and sterile rod approximately 1.7 cm in length and 1.45 mm in diameter.

Concomitant Measures

Advise patients to maintain sun and light protection measures during treatment with SCENESSE to prevent phototoxic reactions related to EPP.

Skin Monitoring

Advise patients that darkening of pre-existing nevi and ephelides may occur with use of SCENESSE. A full body skin examination is recommended twice yearly to monitor pre-existing and new skin pigmentary lesions.

Expelled Implant
Advise patients to contact their healthcare provider if the implant is expelled.

Dressing removal

Advise patients that the dressing can be removed after 24 hours.

Insertion Site Care and Monitoring
Advise patients to monitor the insertion site after dressing removal and to report any reaction observed at the site to their healthcare provider.