The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
Erythropoietic protoporphyria (EPP) is a rare inherited autosomal recessive metabolic disorder that typically manifests in early childhood as severe painful photosensitivity. EPP is caused by mutations in the ferrocheletase (FECH) gene which causes impaired activity of FECH, a crucial enzyme involved in heme production. Photosensitivity usually occurs 1 to 20 minutes after direct exposure to the sun. Patients experience severe burning, typically on hands and face, which is often followed by swelling and redness. This pain can last for several days and usually does not response to pain medications, including narcotic analgesics. Prior to approval of Scenesse (afamelanotide), there were no effective treatment options for EPP. Several treatments (such as beta carotene, N-acetyl-L-cysteine, and vitamin C) have been described in literature; however, show little to no benefit.
On October 8, 2019, the U.S. Food & Drug Administration (FDA) approved Scenesse (afamelanotide) to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP). Scenesse (afamelanotide) is melanocortin 1 receptor (MC1-R) agonist indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from EPP. Scenesse (afamelanotide) is a subcutaneous implant that is administered every 2 months, by a healthcare professional.
The FDA approved Scenesse (afamelanotide) based on evidence from three clinical trials (Trial 1/ NCT 01605136, Trial 2/ NCT00979745 and Trial 3/ NCT01097044) of 244 adult patients 18-74 years of age with EPP. The trials were conducted at 22 sites in US and Europe. Three vehicle-controlled, parallel-group clinical trials 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. Patients were eligible if they were at least 18 years of age, had biochemically confirmed EPP, and did not have clinically significant hepatic or other organ dysfunction, skin cancer, or premalignant lesions or other photodermatoses. Patients with a history of drug or alcohol abuse and pregnant women were not eligible for the trial.
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.
In Trial 3 patients were randomized to receive a total of three Scenesse or vehicle implants administered subcutaneously every 2 months and were followed for 180 days. Data from this trial were used primarily for assessment of side effects. Adverse events that occurred during the study period were generally mild to moderate in severity; in both trials, the most common adverse events were headache, nausea, nasopharyngitis, and back pain. Implant site reactions were more common in the Scenesse (afamelanotide) group (21%) compared to the vehicle group (10%). In the Scenesse (afamelanotide) group, the most common implant site reaction was implant site discoloration (10%).
As per the FDA approved package insert Scenesse (afamelanotide) carries a warning for skin monitoring. Scenesse (afamelanotide) may lead to generalized increased skin pigmentation and darkening of pre-existing nevi and ephelides because of its pharmacologic effect. As per the labeling, a full body skin examination (twice yearly) is recommended to monitor pre-existing and new skin pigmentary lesions.
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
I. Scenesse (afamelanotide) is medically necessary in adults to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP) when all of the following criteria are met:
A. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist, hematologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis
B. Member has a documented biochemically-confirmed diagnosis of EPP by elevated free erythrocyte protoporphyrin and/or identification of pathogenic variants in ferrochelatase (FECH) on molecular gene testing
C. Member has a history of documented phototoxic cutaneous reactions (e.g. pain, infection, skin maceration, etc.) or there is documentation showing significant impact on quality of life or inability to perform activities of daily living (e.g. going outdoors) without experiencing significant pain due to phototoxic reactions from EPP
II. When Scenesse (afamelanotide) is considered medically necessary, therapy will be approved for 12 months at the following FDA approved dosing:
A. Single implant, containing 16 mg of afamelanotide, will be administered subcutaneously every 2 months by a health care profession who is proficient in the subcutaneous implantation procedure and has completed training prior to administration.
III. Scenesse (afamelanotide) will be continued and approved annually, subject to all of the following medical necessity criteria:
A. Member shows clinical improvement (e.g. improvement in the number of hours of direct exposure to sunlight without pain, decrease in the number/pain/severity of phototoxic reactions, etc.)
B. Member did not experience any unacceptable toxicities such as skin abnormalities from Scenesse (afamelanotide)
C. Member continues to have full body skin examinations to monitor pre-existing and new skin pigmentary lesions and continues to maintain sun and light protection measures during treatment with Scenesse (afamelanotide) to prevent phototoxic reactions related to EPP.
IV. Other uses of Scenesse (afamelanotide) are considered investigational.
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
1. Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med 2015;373:48-59. DOI: 10.1056/NEJMoa1411481
2. Scenesse [package insert]. West Menlo Park, CA: Clinuvel, Inc.; October 2019.
3. Poh-Fitzpatrick MB. Protoporphyria. Medscape Reference. 2016; http://emedicine.medscape.com/article/1104061-overview.
4. Deybach JC, Lecha M, Puy H. Autosomal erythropoietic protoporphyria. Orphanet. July 2013; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79278.
5. Balwani M, Bloomer J & Desnick R. Erythropoietic Protoporphyria, Autosomal Recessive. GeneReviews. 2017; http://www.ncbi.nlm.nih.gov/books/NBK100826/.
6. Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP). American Porphyria Foundation. 2015; http://www.porphyriafoundation.com/about-porphyria/types-of-porphyria/EPP-and-XLP.
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy