On July 30, the U.S. Food and Drug Administration (FDA) approved iobenguane I-131 (Azedra) injection for adult and pediatric patients (12 years and older) with iobenguane scan–positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma (PPGL) who require systemic anticancer therapy.
“Many patients with these ultra-rare cancers can be treated with surgery or local therapies, but there are no effective systemic treatments for patients who experience tumor-related symptoms such as high blood pressure,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Patients will now have an approved therapy that has been shown to decrease the need for blood pressure medication and reduce tumor size in some patients.”
Approval was based on Study IB12B, an open-label, single-arm, multicenter clinical trial in patients 12 years and older with iobenguane scan–positive, unresectable, locally advanced or metastatic PPGL.
Of the 68 evaluable patients, 17 (25%; 95% confidence interval [CI] = 16%–37%) experienced a 50% or greater reduction of all antihypertensive medication for at least 6 months. Overall tumor response (RECIST 1.0) 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 to 4 adverse reactions (≥ 10%) were lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, increased international normalized 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 leukemia.
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.
The FDA granted this application Fast Track, Breakthrough Therapy, and Priority Review designations. Iobenguane I-131 also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of iobenguane I-131 to Progenics Pharmaceuticals, Inc.