Azedra® – Progenics Pharmaceuticals, Inc. – 2018 FDA approval

New Drug Overview – iobenguane I 131 (Azedra®)

On July 30, 2018, the U.S. Food and Drug Administration (FDA) approved iobenguane I 131 (Azedra®) for treatment of adults and adolescents age 12 and older with unresectable pheochromocytoma or paraganglioma that has metastasized or is locally advanced and requires systemic anticancer therapy.  Patients must test positive for the norepinephrine transporter (as determined by an iobenguane scan).  Pheochromocytomas increase the production of epinephrines and norepinephrines, leading to hypertension and symptoms such as headaches, irritability, sweating, rapid heart rate, nausea, vomiting, weight loss, weakness, chest pain or anxiety. When this type of tumor occurs outside the adrenal gland, it is called a paraganglioma. These indications carry a poor prognosis, including a five-year survival rate as low as 12%. Life threatening hypertension can lead to heart failure and stroke. An initial overview is listed below.

Generic Name Brand Name Manufacturer Approval Date Anticipated Availability Accelerated Review
iobenguane I 131 Azedra® Progenics Pharmaceuticals, Inc. July 30, 2018 n/a Yes
Labeled Indication(s)
Treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy
Drug Class Comparative Drugs in Class Route of Administration Dosing Schedule
Therapeutic radiopharmaceutical None – innovator for indication Intravenous Initial dosimetric dose to assess biodistribution for possible therapeutic dose adjustment, followed by 2 therapeutic doses at least 90 days apart.
Mechanism of Action:
Iobenguane I 131 is an I 131 labeled iobenguane.  Because of iobenguane’s ability to bind to the norepinephrine transporter found on pheochromocytoma and paraganglioma (PPGL) tumors, iobenguane I 131 delivers therapeutic radiation directly to cancer cells causes cell death and tumor necrosis.
Clinical Trial Summary (Efficacy):
Study: IB12B open-label, single-arm, multicenter clinical trial

Age: at least 12 years old

Primary Outcome: proportion of patients who experienced a 50% or greater reduction of all antihypertensive medication(s) lasting for at least six months (28 days per month)

Other outcome: Overall tumor response measured by RECIST (Response Evaluation Criteria in Solid Tumors version 1.0)

Initial assessment period: 12 months

Efficacy results are contained in the package insert for all 68 patients receiving a first therapeutic dose.  50 patients received two therapeutic doses administered at least 90 days apart.

·         The primary outcome was achieved for 17 (25%) patients (95% CI: 16% to 37%).

·         Overall response rate (ORR) per RECIST: 15 (22%) patients (95% CI: 14% to 33%)

·         53% of the responders had a duration of response >= 6 months

Warnings and Adverse Effects (AE):
Warning: risk of radiation exposure (radiopharmaceutical), myelosuppression, hypothyroidism, hypertension, renal dysfunction or failure, pneumonitis, embryo-fetal toxicity and risk of infertility.  Myelodysplastic syndrome and acute leukemias were also observed.
AE: The most common grade 3-4 adverse reactions (>= 10%) were lymphopenia (78%), neutropenia (59%), thrombocytopenia (50%), fatigue (26%), anemia (24%), increased INR (18%), nausea (16%), dizziness (13%), hypertension (11%) and vomiting (10%).

NDC

Strength (at calibration time) Volume Presentation Storage

71258-0015-02

1,110 MBq (30 mCi) 2 ml Dosimetric -70°C (-94°F)

71258-0015-22

12,488 MBq (337.5 mCi) 22.5 ml Therapeutic

-70°C (-94°F)

Drug Sales Forecast (in millions):
2018(F) 2019(F) 2020(F) 2021(F) 2022(F) 2023(F) 2024(F)
Azedra® $4 $45 $89 $144 $180 $215 $249

 

References:

Global Data Pharma Intelligence Center https://pharma.globaldata.com Accessed August 7, 2018.

Progenics Pharmaceuticals, Inc Azedra® for health care professionals https://azedra.com/healthcare-providers/ Accessed August 7, 2018.

Progenics Pharmaceuticals, Inc. Press Release https://progenicsgc.gcs-web.com/news-releases/news-release-details/progenics-pharmaceuticals-announces-fda-approval-azedrar  Accessed August 7, 2018.

RJ Health Systems Inc Reimbursement Codes https://www.reimbursementcodes.com Accessed August 7, 2018.

U.S. Food and Drug Administration Drugs@FDA: FDA Approved Drug Products Product Labeling https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209607s000lbl.pdf  Accessed August 7, 2018.

U.S. Food and Drug Administration FDA News Release https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm615155.htm Accessed August 7, 2018.


Additional, recent FDA approvals include

Nivestym – Second biosimilar to Filgrastim

Fulphilia – First Biosimilar to Pegfilgrastim 

For a review of the 2018 drug pipeline please click here.