Azedra (iobenguane I-131) Form

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Azedra (iobenguane I-131) - Medical Policy
Updated Revision Effective: February 1, 2024 Policy Number:

UM726POL

Approval Date: 12/20/2023

Line(s) of Business:

Commercial
Medicare Advantage
Medicaid (BeHealthy)

Description

Azedra is a novel version of the radiopharmaceutical iobenguane I 131 intended for treatment of locally advanced or metastatic, scan (+) unresectable pheochromocytoma and paraganglioma, PPGL. Following intravenous administration, Azedra is taken up and accumulates within PPGL cells, and radiation resulting from radioactive decay of I 131 causes cell death and tumor necrosis. Azedra is considered to be a radioactive therapeutic agent.

 Line of Business

Commercial:
Refer to criteria under Policy section in this medical policy.

Medicaid – BeHealthy:
Refer to criteria under Policy section in this medical policy. There are no MassHealth guidelines for Azedra (iobenguane I-131).

Medicare:
Health New England follows Local Coverage Determination (LCD) Chemotherapy Drugs and their Adjuncts (L37205) for Azedra, which is a National Comprehensive Cancer Network (NCCN) category 2A treatment. https://www.cms.gov/medicare-coverage-database/search.aspx

Policy

Policy:

I. Criteria for Approval of Azedra (iobenguane I 131):

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A) Health New England considers Azedra medically necessary for the treatment of Pheochromocytoma or Paraganglioma in members who meet the following criteria for commercial and Medicaid:

1. The member is 12 years or older.
2. Target lesions are confirmed by an iobenguane scan.
3. Pheochromocytoma/Paraganglioma is locally advanced or metastatic. a. In the absence of metastatic disease, documentation of the reason for inoperability
4. Progression of disease on prior therapy for PPGL OR documentation of why the member is not a candidate for chemotherapy

5. Member has had an administration of inorganic iodine.

   B) There are no MassHealth guidelines for Azedra. The above criteria applies.

   C) Health New England follows Local Coverage Determination (LCD) Chemotherapy Drugs and their Adjuncts (L37205) for Azedra, which is a National Comprehensive Cancer Network (NCCN) category 2A treatment. LCD - Chemotherapy Drugs and their Adjuncts (L37205) (cms.gov)

   II. Required Documentation:

   A. Documentation of pathologically diagnosed Pheochromocytoma or Paraganglioma B. Documentation of positive iobenguane scan C. In the absence of metastatic disease, documentation of the reason for inoperability

   III. Azedra (iobenguane I 131) is considered experimental and investigational for the following:
   a. All other indications including neuroblastoma and gastroenteropancreatic neuroendocrine tumors b. Any use of Azedra not in accordance with FDA approved dosing of one dosimetric dose followed by two therapeutic doses administered 90 days apart c. Administration by a physician not qualified by training and experience in the safe administration and handling of radiopharmaceuticals including all premedication, concomitant medications and management of adverse reactions d. Members on concomitant drugs that reduce catecholamine uptake or deplete catecholamine stores. [Examples of drugs that prevent uptake of catecholamine by tissues include Cocaine, Guanethidine (Ismelin), Bretylium, Imipramine (Tofranil), Chlorpromazine (Thorazine & Largactil), and Dibenzyline (Phenoxybenzamine).] e. Severe renal impairment (creatinine clearance < 30)

   IV. Contraindications:

   A. Pregnancy B. Severe Renal Failure, Creatinine clearance < 30 C. Platelet count less than 80,000/mcl or absolute neutrophil count is less than 1,200/mcl D. History of external beam radiation to > 25% of bone marrow E. Liver dysfunction with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.5 times the upper limit of normal or total bilirubin > 1.5 times the upper limit of normal

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F. History of hepatitis or chronic alcohol abuse G. History of systemic radiotherapy resulting in myelosuppression within three months of proposed Azedra administration

Policy Guidelines and Definitions

Definitions:

Dosimetry: The role of radiation dosimetry in targeted radionuclide therapy is to determine specifically, for each patient, the administered amount of the radiopharmaceutical that will most effectively treat the patient’s disease while avoiding absorbed doses that damage normal tissues. Individualized radiation dosimetry is critical for planning the most effective and safest targeted radionuclide therapy for each patient.

Radiopharmaceutical: A pharmaceutical drug that contains radioactive isotopes and can be used for diagnostic and therapeutic purposes.

Paraganglioma: A tumor outside of the adrenal gland that develops in certain nerve cells.

Pheochromocytoma: A tumor of the adrenal gland.

Definitions for NCCN Categories: The specific definitions of the NCCN categories for recommendations are the following:  Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate;  Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate;  Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate;  Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

Coding Guidance

Code
Description
PA A9530 Iodine i-131, iobenguane, 1 millicurie Yes

CPT® Copyright 2023 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

Note: CPT/HCPCS codes are included for informational purposes and may not be all inclusive. Inclusion or exclusion of a CPT/HCPCS code(s) does not signify or imply that the service described by the code is a covered or non-covered health service. Benefit coverage for health services is determined by the member’s specific benefit plan document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to reimbursement or guarantee of payment. Other policies and coverage determination guidelines may apply.

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References

REFERENCES:

UpToDate search updated November 27, 2023

Azedra (n.d.). [Website]. Retrieved from: https://azedra.com/healthcare-providers/

ClinicalTrials.gov (n.d.) A study evaluating ultratrace Iobenguane I131 in patients with malignant relapsed/refractory pheochromocytoma/paraganglioma. Retrieved from https://clinicaltrials.gov/ct2/show/NCT00874614

ClinicalTrials.gov (n.d.). Phase 1 study of iobenguane (MIBG) I 131 in patients with malignant pheochromocytoma/paraganglioma. Retrieved from https://clinicaltrials.gov/ct2/show/NCT00458952

Dasari, A., Shen, C., Halperin, D., Zhao, B., Ahou, S., Xu, Y., Shih, T, Yao, J.C. (2017) Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncology, 3(10): 1335-1342. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28448665/

Gonias S, Goldsby R, Matthay, K.K., Hawkins, R., Price, D., Huberty, J., Damon, L., Linker, C., Sznewajs, A., Shiboski, S., Fitzgerald, P. (2009). Phase II Study of High-Dose [131I]Metaiodobenzylguanidine Therapy for Patients With Metastatic Pheochromocytoma and Paraganglioma. Journal of Clinical Oncology, 1; 27(25): 4162–4168. DOI 10.1200/JCO.2008.21.3496

Hamidi, O., Young Jr, W.F., Iniguez-Ariza, N.M., Kittah, N.E., Gruber, L., Bancos, C., Tamhane, Sl, Bancos, I. (2017) Malignant pheochromocytoma and paraganglioma: 272 patients over 55 years. The Journal of Clinical Endocrinology & Metabolism 102(9): 3296-3305. Retrieved from

https://academic.oup.com/jcem/article/102/9/3296/3866790

National Cancer Institute (n.d.) Pheochromocytoma and paraganglioma treatment (PDQ)- Health professional version. Retrieved from https://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq

Society of Nuclear Medicine and Molecular Imaging (n.d.). Fact sheet: What is radiation dosimetry? Accessed at https://www.snmmi.org/AboutSNMMI/Content.aspx?ItemNumber=31086

U.S Food & Drug Administration (2018). Drug approval package: Azedra (iobenguane I 131). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209607Orig1s000TOC.cfm

https://www.nccn.org/guidelines/guidelines-process/development-and-update-of-guidelines

Policy Implementation

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Approved by the Medical and Pharmacy Policy Committee

Kate McIntosh MD MBA

Chief Medical Officer

Saad Usmani MD MBA

Medical Director

Date Update 7/2022  Under Azedra definition, added: scan (+) unresectable  Under III D added names of medications
Under IV Contraindications, added letters E, F, and G 11/2023 New Template. References updated 1/2024 Added Line of Business section

Medical Criteria Disclaimer

Property of Health New England. All rights reserved. The treating physician or primary care provider must submit to Health New England the clinical evidence that the patient meets the criteria for the treatment, testing or surgical procedure. Without this documentation and information, Health New England will not be able to properly review the request for prior authorization. The clinical review criteria reflect how Health New England determines whether certain services or supplies are medically necessary. Health New England established the clinical review criteria based upon a review of currently available clinical information (including clinical outcome studies in the peer-reviewed published medical literature, regulatory status of the technology, evidence-based guidelines of public health and health research agencies, evidence-based guidelines and positions of leading national health professional organizations, views of physicians practicing in relevant clinical areas, and other relevant factors).
Health New England expressly reserves the right to revise these conclusions as clinical information changes, and welcomes further relevant information. Each benefit program defines which services are covered. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered and/or paid for by Health New England, as some programs exclude coverage for services or supplies that Health New England considers medically necessary. If there is a discrepancy between this guideline and a member's benefits program, the benefits program will govern. In addition, coverage may be mandated by applicable legal requirements of a state, the Federal Government or the Centers for Medicare & Medicaid Services (CMS) for Medicare and Medicaid members. All coding and web site links are accurate at time of publication. Health New England has adopted the herein policy in providing management, administrative and other services to its Health Plan.