IOBENGUANE I-131 - Generic Drug Details

What are the generic sources for iobenguane i-131 and what is the scope of patent protection?

Iobenguane i-131 is the generic ingredient in one branded drug marketed by Progenics Pharms Inc and is included in one NDA. Additional information is available in the individual branded drug profile pages.

Summary for IOBENGUANE I-131

US Patents:	0
Tradenames:	1
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	12
Clinical Trials:	16
What excipients (inactive ingredients) are in IOBENGUANE I-131?	IOBENGUANE I-131 excipients list
DailyMed Link:	IOBENGUANE I-131 at DailyMed

Recent Clinical Trials for IOBENGUANE I-131

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Jubilant DraxImage Inc.	Phase 2
Mayo Clinic	Early Phase 1
National Cancer Institute (NCI)	Early Phase 1

See all IOBENGUANE I-131 clinical trials

US Patents and Regulatory Information for IOBENGUANE I-131

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Progenics Pharms Inc	AZEDRA	iobenguane i-131	SOLUTION;INTRAVENOUS	209607-001	Jul 30, 2018		DISCN	Yes	No

Iobenguane I-131 Market Dynamics, Financial Trajectory, Patent Exclusivity, and Competitive Risk

Last updated: September 4, 2026

Iobenguane I-131, marketed as Azedra, is a targeted radiopharmaceutical approved for adults with iobenguane scan-positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy. The product has a narrow commercial market, high treatment complexity, orphan-drug exclusivity, and limited direct competition. Its financial opportunity is constrained by the small patient population, specialist-center requirements, radioactive-isotope logistics, and competition from off-label high-dose I-131 MIBG therapy.

Lantheus Holdings acquired Azedra through its 2020 acquisition of Progenics Pharmaceuticals. Lantheus does not separately report Azedra revenue in its public financial filings, indicating that the product is immaterial relative to PYLARIFY, DEFINITY, and the company’s other diagnostic and therapeutic radiopharmaceutical businesses (Lantheus Holdings, 2024).

What is iobenguane I-131 and who manufactures Azedra?

Iobenguane I-131 is an iodine-131-labeled norepinephrine analogue. It is taken up by norepinephrine transporters expressed on many pheochromocytoma and paraganglioma cells. The radioactive iodine delivers beta radiation to tumor tissue.

Azedra is supplied as an intravenous radiopharmaceutical and is administered in two therapeutic doses. The FDA-approved regimen includes a dosimetric dose followed by therapeutic administrations separated by at least 90 days. Patients receive thyroid blockade to reduce uptake of radioactive iodine by the thyroid gland (FDA, 2018).

Product	Active ingredient	Manufacturer/owner	FDA status	Primary use
Azedra	Iobenguane I-131	Lantheus Holdings, formerly Progenics	FDA-approved July 30, 2018	Unresectable, locally advanced or metastatic pheochromocytoma/paraganglioma
High-dose I-131 MIBG	Iobenguane I-131	Multiple hospital and nuclear-medicine sources	Often used off label or under institutional protocols	MIBG-avid neuroendocrine tumors
Lutathera	Lutetium-177 dotatate	Novartis	FDA-approved	Somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumors
Pluvicto	Lutetium-177 vipivotide tetraxetan	Novartis	FDA-approved	PSMA-positive metastatic prostate cancer

Azedra is distinct from lutetium-based radioligand therapies because its target is the norepinephrine transporter rather than somatostatin receptor 2 or prostate-specific membrane antigen.

What is the FDA regulatory status of iobenguane I-131?

The FDA approved Azedra under the accelerated approval pathway on July 30, 2018. The indication covers adults with iobenguane scan-positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy (FDA, 2018).

The approval was supported primarily by Study IB12B, a multicenter clinical study evaluating blood pressure reduction and tumor response. The FDA label reports that 25% of patients achieved a clinically meaningful reduction in all three antihypertensive medication categories, while 17% achieved a reduction in antihypertensive medication use sustained for at least six months. The objective response rate was limited, consistent with the product’s role as a disease-control and symptom-management therapy rather than a broadly active cytotoxic drug.

Azedra carries important radiation-safety requirements. Treatment must be delivered by personnel trained in therapeutic nuclear medicine, with radiation monitoring, patient-release controls, and procedures for handling radioactive waste and bodily fluids. These requirements reduce the number of hospitals able to administer the product.

How does the FDA label affect market access?

The label restricts use to patients with demonstrable iobenguane uptake. Patients with non-MIBG-avid tumors are ineligible. The treatment is also unsuitable for some patients with poor marrow reserve, severe renal impairment, or other conditions that increase radiation toxicity.

The main safety issues include:

• Thrombocytopenia, neutropenia, and anemia
• Radiation exposure to caregivers and healthcare workers
• Renal toxicity
• Hypothyroidism
• Infertility risk
• Secondary malignancies, including myelodysplastic syndrome and acute leukemia

These restrictions limit prescribing outside high-volume neuroendocrine tumor and nuclear-medicine centers.

When does iobenguane I-131 lose orphan-drug exclusivity?

Azedra received orphan-drug designation before approval. The FDA granted seven years of orphan-drug exclusivity beginning on the approval date. The principal orphan exclusivity period therefore runs from July 30, 2018, through July 30, 2025, subject to the statutory treatment of the endpoint date and any applicable regulatory events (FDA, 2018).

Orphan exclusivity prevents FDA approval of the same drug for the same orphan indication during the exclusivity period, unless the sponsor cannot assure sufficient supply or the competing product is clinically superior. It does not prevent approval of a different drug, a different radioligand, or a product for a different indication.

The end of orphan exclusivity does not automatically create generic competition. A competing manufacturer would still need to establish pharmaceutical quality, radioactive-isotope handling, clinical comparability, and commercial access to qualified treatment centers.

What patents protect Azedra and iobenguane I-131?

Azedra’s commercial protection has relied on a combination of patent rights, orphan exclusivity, formulation and manufacturing know-how, regulatory data, and operational barriers.

The relevant protection categories are:

1. Drug composition and radiolabeling technology. These rights may cover the iobenguane molecule, iodine-131 labeling, precursor materials, or the finished radiopharmaceutical.
2. Treatment methods. Claims may cover administration schedules, patient selection, blood-pressure reduction, tumor response, and dosimetry.
3. Manufacturing and quality control. Radioactive products require controls over specific activity, radionuclidic purity, sterility, stability, and release testing.
4. Distribution and handling systems. These may include validated packaging, shipment timing, dose calibration, and radiation-safety processes.

Public patent databases associate Progenics and related entities with patents covering iobenguane I-131 treatment and radiopharmaceutical production. Patent term must be evaluated patent by patent because expiration can differ based on filing date, terminal disclaimers, patent-term adjustment, and any patent-term extension.

The commercial conclusion is more important than a single patent date: the end of orphan exclusivity is earlier than the expected expiration of at least some patent rights associated with the product and its use. Patent protection therefore remains relevant after the orphan period, but its value depends on claim scope and whether a competing product can avoid the asserted claims.

What is the Orange Book status of Azedra?

Azedra is an FDA-approved prescription drug subject to FDA drug-listing and patent-transparency requirements. Orange Book relevance depends on whether the sponsor has listed patents that claim the drug, its approved use, or a method of using the drug.

An Abbreviated New Drug Application applicant seeking approval of a therapeutically equivalent iobenguane I-131 product would need to address any applicable listed patents through Paragraph I, II, III, or IV certifications. Method-of-use patents may be addressed through a section viii statement if the applicant omits the patented use from its labeling.

A radiopharmaceutical competitor may also pursue a full 505(b)(2) application rather than a conventional ANDA. That route could be more practical if the product has differences in formulation, dosing, manufacturing, dosimetry, or clinical use. It would not eliminate patent litigation risk.

Have companies filed Paragraph IV challenges against Azedra?

There has been no widely disclosed Paragraph IV litigation comparable to the litigation surrounding high-revenue small-molecule drugs. The limited patient population and technical manufacturing requirements reduce the expected return from a conventional generic challenge.

The absence of a public Paragraph IV case does not eliminate future entry risk. A challenger could pursue:

• An ANDA with a Paragraph IV certification
• A 505(b)(2) application for a differentiated iobenguane I-131 product
• A hospital-manufactured or institutionally prepared radiopharmaceutical pathway, where legally and operationally available
• A competing MIBG-targeted therapy using a different formulation or dosing design

The strongest barriers are likely to be clinical supply, radiochemical manufacturing, isotope availability, quality validation, and treatment-center economics rather than orphan exclusivity alone.

What is the financial trajectory for Azedra?

Lantheus has not separately disclosed Azedra revenue in its recent annual reports. That reporting decision prevents a reliable standalone revenue series and indicates that Azedra is not a material driver of consolidated results.

Lantheus’s financial growth has been led by larger products, particularly PYLARIFY and DEFINITY. PYLARIFY became the company’s principal growth engine after its 2021 approval for prostate cancer imaging. Azedra remains strategically relevant as a therapeutic radiopharmaceutical but has a much smaller revenue base and a narrower addressable market (Lantheus Holdings, 2024).

Azedra’s commercial economics

Factor	Effect on revenue
Rare disease population	Limits annual treatment volume
Two-dose treatment course	Raises revenue per treated patient but reduces repeat-use frequency
Specialist-center requirement	Restricts geographic penetration
Radioactive half-life and shipment timing	Increases inventory and logistics costs
Reimbursement complexity	Can delay adoption
High-dose I-131 MIBG alternatives	Limits pricing power
MIBG-positive patient selection	Narrows eligible population
Lantheus commercial infrastructure	Improves access to nuclear-medicine customers
Orphan status	Supports premium pricing and focused market development

Azedra’s revenue trajectory is therefore best characterized as niche and capacity-constrained, rather than a high-growth platform product. Its strategic value may exceed its direct sales contribution because it gives Lantheus experience in therapeutic radiopharmaceutical manufacturing, reimbursement, radiation logistics, and oncology-center contracting.

How large is the addressable market for iobenguane I-131?

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Only a subset of patients has advanced disease, requires systemic treatment, and demonstrates sufficient MIBG uptake for Azedra.

The practical treatment funnel is narrower than the epidemiological population:

1. Patients must have unresectable or metastatic disease.
2. Their tumors must be iobenguane scan-positive.
3. They must require systemic anticancer therapy.
4. Their marrow, renal function, and overall condition must support radioactive treatment.
5. They must have access to an authorized or capable nuclear-medicine center.

This creates a small, concentrated market. Pricing may be high relative to conventional oncology drugs, but total annual revenue remains limited by patient volume and treatment-center throughput.

What generic launch scenarios exist for Azedra?

The most plausible entry scenarios are:

Scenario 1: No near-term conventional generic

A competitor may decide that the market is too small to justify radioactive manufacturing, clinical development, and distribution infrastructure. Azedra could retain practical market exclusivity despite the end of orphan exclusivity.

Scenario 2: 505(b)(2) competitive product

A sponsor could develop a product with a modified formulation, dose, labeling strategy, or manufacturing process. This route could produce competition without proving complete sameness to Azedra.

Scenario 3: Off-label high-dose MIBG substitution

Hospitals may use noncommercial or institutionally sourced I-131 MIBG protocols where permitted. This is the most direct economic substitute but may not provide the same FDA-approved labeling, standardized dosing, commercial support, or reimbursement certainty.

Scenario 4: Targeted radioligand displacement

New radioligands directed at neuroendocrine tumors could compete for nuclear-medicine capacity, oncology budgets, and physician attention. These products would not be direct generic substitutes but could reduce treatment slots available for Azedra.

How strong is the Azedra patent estate?

Azedra’s patent estate is moderately defensible from a commercial perspective but less secure than the estate of a high-volume drug with multiple composition-of-matter patents.

Its strengths are:

• Specialized radiopharmaceutical manufacturing
• Method-of-use and dosing claims
• Limited number of capable competitors
• Technical difficulty of proving equivalence
• Regulatory and radiation-safety infrastructure

Its weaknesses are:

• Small market size limits litigation economics
• Orphan exclusivity has ended or is at its endpoint
• Alternative MIBG treatment protocols may avoid product-specific claims
• Different radioligands can compete without infringing iobenguane claims
• Hospital and academic radiopharmacy capabilities may create noncommercial alternatives

Patent strength should therefore be measured by the ability to prevent practical substitution, not only by the number of listed patents.

What licensing deals and ownership changes affect Azedra?

Progenics developed Azedra and commercialized the product before its acquisition by Lantheus. Lantheus completed the acquisition of Progenics in 2020, bringing Azedra into its radiopharmaceutical portfolio (Lantheus Holdings, 2020).

The transaction changed Azedra’s commercial context. Progenics had a more concentrated oncology pipeline, while Lantheus had a larger diagnostic imaging infrastructure, sales organization, payer relationships, and nuclear-medicine customer base. Lantheus has not identified Azedra as a separately reported major revenue segment in its subsequent financial reporting.

Key Takeaways

• Azedra is FDA-approved iobenguane I-131 for adults with MIBG-positive advanced pheochromocytoma or paraganglioma.
• Lantheus owns and markets the product following its acquisition of Progenics.
• Seven-year orphan-drug exclusivity began July 30, 2018, with the principal period ending in 2025.
• Lantheus does not separately disclose Azedra revenue, indicating a small contribution to consolidated sales.
• Market size is constrained by disease rarity, MIBG positivity, treatment eligibility, and specialist-center capacity.
• No major publicly disclosed Paragraph IV challenge has materially disrupted the product.
• Generic competition is less likely to emerge through a simple ANDA than through a 505(b)(2) product, off-label high-dose MIBG, or another targeted radioligand.
• The product’s strongest commercial protections are technical manufacturing, radiation logistics, clinical know-how, and treatment-center infrastructure.
• Azedra is strategically relevant to Lantheus’s therapeutic radiopharmaceutical portfolio but is not a principal financial growth driver.

FAQs

Is iobenguane I-131 the same as MIBG?

Yes. Iobenguane is also known as metaiodobenzylguanidine, or MIBG. Azedra is the commercial I-131-labeled form approved for therapeutic use in selected pheochromocytoma and paraganglioma patients.

Can Azedra be used for neuroblastoma?

Azedra’s FDA indication is for adult pheochromocytoma and paraganglioma. Use in neuroblastoma is outside that labeled indication and depends on clinical judgment, applicable evidence, and institutional practice.

Does Azedra have a biosimilar competitor?

No. Azedra is a radiolabeled small-molecule drug, not a biologic. The relevant competitive pathways are generic, 505(b)(2), institutionally prepared MIBG, and other radioligand therapies.

Why is Azedra difficult to manufacture?

Manufacturing requires radioactive iodine handling, radiochemical synthesis, sterile production, radionuclidic and radiochemical purity testing, dose calibration, time-sensitive shipment, and radiation-safety controls. These requirements are more demanding than those for most conventional oral oncology drugs.

Does the end of orphan exclusivity guarantee a generic Azedra launch?

No. Orphan exclusivity is only one protection. A competitor would still face patent claims, FDA requirements, radioactive manufacturing controls, clinical validation, reimbursement barriers, and a small commercial market.

References

1. Food and Drug Administration. (2018). Azedra (iobenguane I 131) prescribing information. U.S. Department of Health and Human Services.

2. Food and Drug Administration. (2018, July 30). FDA approves iobenguane I 131 for rare tumors. U.S. Department of Health and Human Services.

3. Lantheus Holdings, Inc. (2020). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the fiscal year ended December 31, 2020. U.S. Securities and Exchange Commission.

4. Lantheus Holdings, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the fiscal year ended December 31, 2023. U.S. Securities and Exchange Commission.

5. Pryma, D. A., Chin, B. B., Noto, R. B., et al. (2019). Efficacy and safety of high-specific-activity iodine-131 metaiodobenzylguanidine therapy in patients with advanced pheochromocytoma or paraganglioma. Journal of Nuclear Medicine, 60(5), 623-630.