Phase 2 Azedra Data Presented at ENDO Meeting

At the Endocrine Society (ENDO) Annual Meeting in Chicago, Illinois this weekend, Progenics Pharmaceuticals, Inc. presented biochemical tumor marker data from its pivotal Phase 2 trial of iobenguane I 131 (Azedra) in patients with malignant, recurrent, and/or unresectable pheochromocytoma and paraganglioma.

The data was reviewed in an oral presentation by Dr Camilo Jimenez, Associate Professor, Department of Endocrine Neoplasia and Hormonal Disorders at the University of Texas M. D. Anderson Cancer Center.

The presentation, titled “AZEDRA (iobenguane I 131) in Patients with Metastatic and/or Recurrent and/or Unresectable Pheochromoctyoma or Paraganglioma: Biochemical Tumor Marker Results of a Multicenter, Open-Label Pivotal Phase 2 Study,” and examined results from the Phase 2 open-label, multi-center trial that was conducted under a Special Protocol Assessment (SPA) with the FDA.

The targeted, high-specific-activity radiotherapeutic candidate is currently in development for the treatment of the rare neuroendocrine tumors (NETs), and Progenics New Drug Application for it was granted Priority Review by the U.S. Food and Drug Administration (FDA) in December. An action date has been set for April 30, 2018 under the Prescription Drug User Fee Act (PDUFA).

“The compelling results from this pivotal trial formed the basis of our New Drug Application for AZEDRA, which was accepted for review by the FDA at the end of 2017,” Mark Baker, Chief Executive Officer of Progenics said in a press release. “We are eagerly awaiting the FDA’s action date at the end of April for our innovative radiopharmaceutical treatment. AZEDRA has the potential to be the first FDA-approved therapy to address the high unmet need of patients with malignant pheo and para.”

Tumor biomarkers were analyzed in patients who had individual tumor biomarkers above 1.5-times the upper limit of normal (ULN) at baseline. The primary endpoint of the clinical trial was met, as patients with pheochromocytoma and paraganglioma who were administered iobenguane I 131 achieved a 50% of greater reduction of all antihypertensive medication for at least 6 months.

The overall tumor biomarker response correlated with responder status for those who met the study’s primary endpoint (r=0.31, p=0.011) and objective tumor response (r=o.35, p=0.006). The biomarkers evaluated were Chromogranin A (CgA, serum), Normetaneprine (NM, serum and urine) and Norepinephrine (NE, serum and urine).

The best response (CR/PR) was observed at 12 months following the first therapeutics dose of the drug in urine and serum NE with rates of 42.1% and 31.0%, respectively. Additionally, serum CgA showed the best response rate of 67.9% at 12 months.

“In this pivotal study of AZEDRA in pheo and para patients, the overall tumor biomarker response correlated significantly with responder status with both the primary and secondary endpoints,” said Dr Jimenez.

“AZEDRA has already been shown to have a significant positive impact on the cardiovascular symptoms associated with pheochromocytoma and paraganglioma. It has also demonstrated objective antitumor effects as measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The biochemical tumor marker data presented today provides further evidence of AZEDRA’s potential to offer a meaningful treatment option for patients with these life-threatening tumors.”

In addition to meeting its primary endpoint, the trial reported favorable results from a key secondary endpoint that evaluated the proportion of patients with overall tumor response as measured by RECIST (Response Evaluation Criteria In Solid Tumors).

The candidate was proven to be safe and generally well-tolerated in the study, ad the efficacy exhibited appears consistent with what the FDA deems acceptable for drugs that receive approval.

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