Molecular Insight Pharmaceuticals Presents Azedra Efficacy Data in Neuroendocrine Tumors
Cambridge, MA, October 5, 2009 – Molecular Insight Pharmaceuticals, Inc. (NASDAQ: MIPI) today reported one-year follow-up data from a Phase I dose-escalation clinical study of Azedra™ demonstrating a positive safety profile and durable objective tumor responses in patients with neuroendocrine cancers, pheochromocytoma and paraganglioma. The study was designed to evaluate the safety and identify the maximum tolerated dose (MTD) of Azedra, as well as to collect clinical data on efficacy. These data were presented on October 2, 2009, at the North American Neuroendocrine Tumor Society (NANETS) 2009 Neuroendocrine Tumor Symposium in Charlotte, North Carolina. Azedra (UltratraceTM iobenguane I 131) is Molecular Insight’s lead oncology targeted radiotherapeutic using the Company’s proprietary radiolabeling technology platform.
In 12-month data reported today, a single dose of Azedra was shown to be well tolerated by patients, and toxicities were predictable and manageable. Additionally, Azedra demonstrated clinical benefit, stabilizing or reducing tumor volumes in a majority of patients. Twenty-one patients were treated at escalating dose levels from 6 to 9 mCi/kg. Objective tumor response according to Response Criteria in Solid Tumors (RECIST) was obtained every three months. Best confirmed overall response per RECIST was partial response (PR) for three patients (14%), stable disease for 14 (67%), progressive disease for two (10%), and not evaluable for two (10%) who had no follow-up scans. All three patients with PR demonstrated this response at the first post-therapy visit at three months and sustained the response through 12 months.
“Currently, there are no approved treatments in the United States for patients with metastatic neuroendocrine tumors, so a targeted radiotherapeutic such as Azedra that could provide a more potent, effective therapy would be a significant therapeutic advancement,” commented R. Edward Coleman, M.D., of Duke University Medical Center, an author and investigator on the study. “These results at one year after therapy demonstrate that Azedra therapy may potentially benefit many patients who have metastatic pheochromocytoma or paraganglioma.”
Data reported today provide long-term confirmation of preliminary Phase I clinical findings presented at the 2008 American Society of Clinical Oncology (ASCO) Annual Meeting. In June 2009, Molecular Insight Pharmaceuticals initiated a single-arm, pivotal Phase 2 clinical trial for Azedra for the treatment of malignant pheochromocytoma under a Special Protocol Assessment (SPA) by the U.S. Food and Drug Administration (FDA). In addition, Azedra has been granted Orphan Drug designation and Fast Track status by the FDA. Under these programs, Molecular Insight plans to file a New Drug Application (NDA) based on the Phase 2 data and anticipates expedited FDA review of its application.
Phase I Study Overview
The Phase I dose-escalation study was designed to identify the maximum tolerated dose (MTD) of Azedra and to evaluate the safety and efficacy in patients with pheochromocytoma/ paraganglioma. The study results reported today support a maximum tolerated dose of 8 mCi/kg (maximum 600 mCi). Related adverse events were primarily hematologic or gastrointestinal, as expected.
Patient evaluations were scheduled at 3, 6, 9, and 12 months. Long-term follow-up will continue every six months through 5 years after treatment with Azedra. In addition to RECIST criteria, other efficacy evaluations included tumor biomarker response. Hypertension measurement was performed as part of safety evaluations and anti-hypertensive medication taper, discontinuation or changes were not a pre-specified endpoint in this study. Since hypertension typically occurs in more than 90 percent of pheochromocytoma/paraganglioma patients, changes in anti-hypertensive medication from baseline use, as a measure of clinical benefit and tumor response, were also evaluated.
While tumor markers in these patients are known to show frequent and considerable variability in values, many patients with elevated baseline tumor markers showed decreases, with many having normalization of these levels at a post-therapy visit that was consistent with preliminary findings reported previously [ASCO, 2008]. For example, at six months post-therapy, vanillylmandelic acid levels were normalized or decreased by at least 50% for four of the 11 evaluable patients with elevated baseline values. Furthermore, five of 15 (33%) patients on anti-hypertensive medications at time of therapy reduced or discontinued use of these medications following treatment.
Significant side effects observed in the trial were thrombocytopenia, neutropenia, dry mouth, salivary gland pain, nausea, vomiting, fatigue and anorexia. The dose-limiting toxicities were neutropenia (2), febrile neutropenia (1), and thrombocytopenia (1). Two patients died within the 12-month efficacy follow-up (hepatic failure, pulmonary embolism), while three died during long-term follow-up; all deaths were considered by the study investigator to be unrelated to Azedra. In this study, the drug demonstrated favorable dosimetry and a predictable safety profile at all doses tested. Per protocol, 8 mCi/kg (maximum 600 mCi) was confirmed as a tolerable dose in adult patients with pheochromocytoma.
Susan Pietropaolo BCC Partners O: 845.638.6290 M: 201.923.2049 E: firstname.lastname@example.org
Posted: October 2009