On 30 July 2018, the US Food and Drug Administration (FDA) approved iobenguane I 131 (AZEDRA, Progenics Pharmaceuticals, Inc.) for adult and paediatric patients (12 years and older) with iobenguane scan-positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.
Approval was based on Study IB12B (NCT00874614), an open-label, single-arm, multicentre clinical trial in patients 12 years and older with iobenguane scan-positive, unresectable, locally advanced or metastatic paraganglioma. Of the 68 evaluable patients, 17 (25%; 95% CI: 16%, 37%) experienced a 50% or greater reduction of all antihypertensive medication for at least six months. Overall tumour response (RECIST v1.0) occurred in 15 patients (22%; 95% CI: 14%, 33%), with 53% achieving a response duration of at least 6 months.
The most common grade 3-4 adverse reactions (≥10%) were lymphopenia, neutropenia, thrombocytopenia, fatigue, anaemia, increased international normalised ratio, nausea, dizziness, hypertension, and vomiting. In the pooled safety population, 6.8% of patients who received a therapeutic dose of iobenguane I 131 developed myelodysplastic syndrome or acute leukaemia.
Iobenguane I 131 is administered in an initial dosimetric dose, followed by two therapeutic doses that are adjusted based on dosimetry. The recommended therapeutic dose is 18,500 MBq (500 mCi) for patients weighing more than 62.5 kg and 296 MBq/kg (8 mCi/kg) for patients 62.5 kg or less.
Full prescribing information for AZEDRA is available here.
FDA granted this application priority review, orphan product, fast track status, and breakthrough therapy designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.