Coverage Policy Manual
Policy #: 2020013
Category: Pharmacy
Initiated: July 2020
Last Review: June 2022
  Afamelanotide (e.g., Scenesse™)

Description:
Erythropoietic protoporhyria (EPP) is an autosomal recessive porphyria that can cause severe sensitivity to sunlight, gallstones, cholestatic hepatitis, and liver damage. EPP is caused by a deficiency of ferrochelatase in the heme biosynthetic pathway. This results in accumulation of protoporphyrin in the bone marrow, red blood cells, plasma, skin, and liver. Severe neuropathic pain is caused when the accumulated phototoxic protoporphyrin is activated by visible light, including sunlight and some artificial light, and triggers singlet oxygen free radical reactions. The pain can last for hours to days. Cholestatic hepatitis and gallstone results from accumulation of protoporphyrin in the liver in amounts that are damaging to hepatocytes and cholangiocytes. Liver damage caused by EPP is rare and affects fewer than 5% of cases. In severe cases, cholestatic hepatitis can progress to liver failure requiring transplantation.
 
Afamelanotide is a synthetic tridecapeptide and structural analog of α-melanocyte stimulating hormone. It is a melanocortin receptor agonist and binds predominantly to melanocortin 1 receptor increasing pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. Afamelanotide increased the production of eumelanin in the skin independently of exposure to sunlight or artificial ultraviolet light sources.
 
Regulatory Status
 
Afamelanotide (e.g., ScenesseTM) was approved by the U.S. Food and Drug Administration (FDA) on October 8, 2019 to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria.
 
On January 1,2021 J7352 will be effective for Afamelanotide (e.g., Scenesse™).  Services billed as of January 1, 2021 and after will be expected to be billed with this code.      

Policy/
Coverage:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Afamelanotide to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria or for any other condition has insufficient evidence to meet primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of Afamelanotide to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria or for any other condition is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 

Rationale:
The FDA approval of Afamelanotide (ScenesseTM) was based on two Phase 3 multicenter, randomized, double-blind, placebo controlled trials. The first study was completed in the European Union and patients received Afamelanotide (ScenesseTM) or placebo for 9 months. The second study was completed in the United States and patients received Afamelanotide (ScenesseTM) or placebo for 6 months. Eligibility criteria were the same in the two trials; patients must be 18 years of age or older, must have a biochemically confirmed erythropoietic protoporphyria, and must not have a 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 females were excluded from the trials. In both studies patients were randomly assigned to receive either an implant formulation of 16 mg of Afamelanotide (ScenesseTM) or a placebo implant formulation in a 1:1 ratio. Implants were inserted in the subcutaneous fat above the iliac crest with a 14-gauge catheter needle and then pushed into the fat tissue with a 16-gauge stylet.
    • In the European Union study, an implant was inserted on days 0, 60, 120, 180, and 240. The primary endpoint was the duration of direct sunlight exposure without pain between 10:00 am and 3:00 pm. Secondary endpoints were combined sun exposure and phototoxic pain, sun exposure, quality of life, photoprovocation, phototoxicity, and safety and tolerability. Patients were required to keep a daily log of the intensity and duration of pain and exposure to sunlight and shade. 74 patients were enrolled in European Union study. 38 patients received the Afamelanotide (ScenesseTM) implant and 36 patients received placebo. The median duration of pain-free time was longer in the Afamelanotide (ScenesseTM) group compared to the placebo (6.0 hours vs. 0.75 hours).
    • In the United States study, an implant was inserted on days 0, 60, and 120. The primary endpoint was the duration of direct sunlight exposure without pain between 10:00 am and 6:00 pm. Secondary endpoints were combined sun exposure and phototoxic pain, sun exposure, quality of life, photoprovocation, phototoxicity, and safety and tolerability. Patients were required to keep a daily log of the intensity and duration of pain and exposure to sunlight and shade. 93 patients were enrolled in the United States study. 48 patients received the Afamelanotide (ScenesseTM) implant and 45 patients received placebo. The median duration of pain free time was longer in the Afamelanotide (ScenesseTM) group compared to the placebo (64.1 hours vs. 40.5 hours).
Mild to moderate adverse events occurred in both study groups and included headache, nausea, nasopharyngitis, and back pain. Serious adverse events in both the Afamelanotide (ScenesseTM) and placebo group were considered by the principal investigator to be unrelated to the study drug.
There was no evidence in either study that Afamelanotide (ScenesseTM) had any impact on gallstones, cholestasis, cirrhosis, or liver failure (Langendonk 2015). Afamelanotide (ScenesseTM) does provide treatment of symptoms in patients with erythropoietic protoporphyria in regard to light exposure. However current evidence does not indicate that high levels of protoporphyrin are affected with Afamelanotide (ScenesseTM) treatment. The evidence for efficacy is insufficient to meet primary coverage criteria.
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2022. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:
11981Insertion, drug delivery implant (i.e., bioresorbable, biodegradable, non-biodegradable)
J3490Unclassified drugs
J3590Unclassified biologics
J7352Afamelanotide implant, 1 mg

References: Department of Health and Human Services.(2018) ) “Erythropoietic protoporphyria.” Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, 11 June 2020 https://rarediseases.info.nih.gov/diseases/4527/erythropoietic-protoporphyria

Langendonk JG, Balwani M, Anderson KE, et al.(2015) Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015; Accessed 10 June 2020 https://www.nejm.org/doi/pdf/10.1056/NEJMoa1411481?articleTools=true

Li MM, Datto M, Duncavage EJ, et al.(2017) Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4-23. doi:10.1016/j.jmoldx.2016.10.002

Richards S, Aziz N, Bale S, et al.(2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424. doi:10.1038/gim.2015.30

SCENESSE (afamelanotide) implant, package insert. West Menlo Park, CA. Clinuvel, Inc.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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