On March 30, 2017 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported that the Company’s registrational Phase 2b trial of its novel radiotherapeutic candidate, AZEDRA (iobenguane I 131) Injection, has achieved its primary endpoint (Press release, Progenics Pharmaceuticals, MAR 30, 2017, View Source [SID1234518338]). The open-label, multi-center study was conducted under a Special Protocol Assessment (SPA) agreement with the Food and Drug Administration (FDA). The trial was designed to evaluate the efficacy and safety of AZEDRA in patients with malignant and/or recurrent pheochromocytoma or paraganglioma, which are rare neuroendocrine tumors. There are currently no approved therapeutics in the U.S. for the treatment of malignant and/or recurrent pheochromocytoma or paraganglioma. AZEDRA has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study met the primary endpoint evaluating the proportion of patients who achieved a 50% or greater reduction of all antihypertensive medication for at least six months. Under the study protocol, the primary endpoint is achieved if the lower limit of the two-sided 95% confidence interval was above 10%.

In the trial, 17 (25%) of the 68 evaluable patients experienced a 50% or greater reduction of all antihypertensive medication for at least 6 months. The lower limit of the 95% confidence interval was 16.15%, thus meeting the primary endpoint. The upper limit of the 95% confidence interval was 36.52%.

Progenics also reported favorable data from a key secondary endpoint, the proportion of patients with overall tumor response as measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. In this highly pre-treated patient population, 92.2% of patients who received at least one AZEDRA therapeutic dose achieved partial response or stable disease.

"The positive data from this trial are clinically meaningful and provide compelling evidence for the use of AZEDRA to treat malignant and/or recurrent pheochromocytoma and paraganglioma," said Dr. Daniel Pryma, Associate Professor of Radiology & Radiation Oncology and Chief, Division of Nuclear Medicine & Clinical Molecular Imaging at the Perelman School of Medicine at the University of Pennsylvania, the trial’s lead investigator. "Without any approved therapeutics in the U.S. for these rare and devastating life-threatening tumors, patients face a poor prognosis and few options. The tumor response data, in particular for the patients that received two doses, along with the adverse event profile from this trial, suggest that AZEDRA has the potential to be a true breakthrough in addressing these difficult-to-treat patients."

Phase 2b Trial Topline Results
The Phase 2b open-label trial was designed to evaluate the efficacy and safety of two therapeutic doses of AZEDRA administered three months apart to patients with malignant relapsed/refractory pheochromocytoma or paraganglioma.

Primary Endpoint: Reduction in Antihypertensive Medications
Under the study protocol, the primary endpoint is achieved if the lower limit of the two-sided 95% confidence interval was above 10%. In order to achieve this primary endpoint, a minimum of 12 of the total 68 evaluable patients must have a 50% or greater reduction of all antihypertensive medication for at least 6 months. As shown in the table below, 17 patients responded, giving a lower limit of the 95% confidence interval of 16.15%, thus meeting the primary endpoint.

Responders (%) Lower bound of
Confidence Interval Upper bound of
Confidence Interval
Overall
(n=68) 17 (25%)

16.15

%

36.52

%

Two Doses
(n=50) 16 (32%)

20.70

%

45.87

%

One Dose
(n=18) 1 (5.6%)

0.0

%

27.65

%



Secondary Endpoint: Overall Tumor Response Assessment per RECIST Criteria
Best response over 12 months after first therapeutic dose

Complete
Response Partial
Response Stable Disease

Progressive
Disease Unable to
Evaluate
Overall
(n=64*) 0

%

23.4

%

68.8

%

4.7

%

3.1

%

2 doses
(n=50) 0

%

30.0

%

68.0

%

2.0

%

0

%

1 dose
(n=14) 0

%

0

%

71.4

%

14.3

%

14.3

%

*4 patients did not have follow-up scans

AZEDRA was generally well tolerated. The most common treatment emergent adverse events were nausea, thrombocytopenia, anemia, fatigue, leukopenia, and neutropenia. These events are consistent with those observed in prior AZEDRA studies.

"We intend to move quickly to complete our New Drug Application submission by mid-2017, as these topline results underscore the potential of AZEDRA in this ultra-orphan indication," said Mark Baker, Chief Executive Officer of Progenics. "We are grateful to the patients and investigators who participated in this trial, and are committed to bringing a new treatment option to this rare cancer population."

Progenics plans to present additional data from this trial at a medical meeting in the second half of 2017.