131I-Iobenguane (MIBG)

Description

¹³¹I-Iobenguane (commonly referred to as ¹³¹I-Metaiodobenzylguanidine or ¹³¹I-MIBG) is a radiopharmaceutical used both diagnostically and therapeutically for primary and metastatic pheochromocytomas and paragangliomas. This compound specifically targets adrenergic tissues, making it effective in localizing these neuroendocrine tumors.

Azedra™ (formerly known as MIP-120T or Ultratrace MIBG), developed by Progenics (previously Molecular Insight Pharmaceuticals, now part of Lantheus since October 2019), represents a more refined version of ¹³¹I-MIBG. It is a highly pure ¹³¹I-labeled compound with purported advantages in imaging quality and therapeutic efficacy. Unlike generic ¹³¹I-MIBG, Azedra uses ultrapure MIBG, although it is not labeled with non-carrier-added (nca) ¹³¹I.

Azedra has received several designations, including orphan drug status and fast-track approval in the US, as well as orphan drug designation for neuroblastoma in the EU. Despite initial delays in development and regulatory submission, the compound completed clinical trials. The FDA accepted Azedra’s New Drug Application (NDA) in December 2017 under Priority Review, and it was approved in July 2018 for treating pheochromocytoma and paraganglioma in patients aged 12 and older.

Clinical Applications

¹³¹I-MIBG is primarily utilized for:

• Diagnostic Imaging: Localization of primary or metastatic pheochromocytoma, paraganglioma, and neuroblastoma. It specifically targets the adrenal medulla and sympathetic nervous tissue. Additional diagnostic applications include neuroendocrine tumors of the gastroenteropancreatic tract, medullary thyroid carcinoma, myocardial ischemia, and cardiomyopathies.
• Therapeutic Use: High doses of ¹³¹I-MIBG are used for treating the aforementioned pathologies, with a typical therapeutic dose ranging from 10 to 20 mCi.

During the 2017 Symposium on Pheochromocytoma and Paraganglioma, phase IIb study results demonstrated Azedra’s ability to produce clinically meaningful and durable responses across multiple endpoints, including radiographic tumor response, biomarker reduction, and overall survival improvement. Beyond pheochromocytomas and paragangliomas, Azedra shows potential for treating neuroblastoma and other neuroendocrine diseases.

Availability

Generic ¹³¹I-MIBG is available from various companies, including:

• BRIT: IOM-50, IOM-50T
• Fuji Film: Pheo®MIBG-I131
• GE Healthcare: ¹³¹I-MIBG
• IBA Molecular (Curium): MIBG-131-D (EU approval 1987) and MIBG-131-T (EU approval 1997)
• Mallinckrodt: Iobenguane ¹³¹I (EU approval 1999)
• Pars Isotope: I-131 MIBG for diagnostic and therapeutic use
• POLATOM: MIBG

Azedra, specifically, has been available in the US since July 2018. Other notable developments include:

• Pharmalucence discontinuing ¹³¹I-Iobenguane Sulfate in 2009.
• BMS/Lantheus discontinuing an authorized form in the EU in 1998.
• Jubilant Draximage and FUJIFILM exploring clinical applications, with ongoing trials for neuroblastoma and pheochromocytoma.

Pricing and Reimbursement: Azedra is priced at approximately $150,000 in the US, with CMS reimbursing $98,150, representing 65% of the treatment cost.

Competition

In imaging, ¹²³I-MIBG is an alternative to ¹³¹I-MIBG, offering superior image quality and reduced radiation exposure to patients. However, its higher cost and limited availability restrict widespread use.

For therapeutic purposes, Azedra provides a more targeted and efficient treatment compared to generic formulations, owing to its purity and formulation advantages. However, its high cost may limit accessibility.

Additional Comments

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that can arise in adrenal glands or near specific blood vessels and nerves. These tumors may be benign or malignant. Current treatment options include surgery, radiation therapy, chemotherapy, ablation, embolization, and targeted therapies.

Clinical trials for ¹³¹I-MIBG are ongoing worldwide, focusing on expanding its use for pheochromocytomas, paragangliomas, and other neuroendocrine disorders. Many of these studies operate independently of pharmaceutical manufacturers, allowing for compassionate-use protocols and improved patient recruitment.

In summary, Azedra distinguishes itself as a US-approved formulation of ¹³¹I-MIBG with enhanced therapeutic efficacy and imaging performance. Despite its advantages, the drug’s high cost and regional availability may impact its global adoption.