SOURCE: Molecular Insight Pharmaceuticals, Inc.

Molecular Insight Pharmaceuticals, Inc.

October 05, 2009 08:35 ET

Molecular Insight Pharmaceuticals Presents Azedra™ 12-Month Efficacy Data From Phase I Clinical Trial in Neuroendocrine Tumors

CAMBRIDGE, MA--(Marketwire - 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 (Ultratrace™ 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.

For the study abstract, please visit the Company's website: http://www.molecularinsight.com/MolecularMedicine/ScientificPosters.aspx

Neuroendocrine Tumors

Neuroendocrine Tumors (NETs) are rare tumors of the nervous and endocrine systems. Until becoming metastatic, they are typically slowly growing and difficult to diagnose. Functional NETs secrete excess hormone, leading to a variety of clinical syndromes, some life threatening and all adversely affecting quality of life.

Pheochromocytomas are NETs that arise from sympathetic nervous system cells in the adrenal gland and often produce catecholamines, resulting in hypertension and other signs and symptoms in many patients. Extra-adrenal pheochromocytomas are called paragangliomas. Approximately 10-15% of patients with pheochromocytoma (pheo)/paraganglioma (para) develop malignant disease with some reports noting >30% of pheos as being malignant. The five-year survival rate for malignant pheo is reported at 50% while patients with metastatic pheochromocytoma have a five-year survival reported between 20-60% with an average of about 35%. Prognosis is worse in patients with metastatic liver or lung lesions where survival is usually less than 2 years. No treatments for pheo/para have been approved in the United States for these rare tumors.

About Azedra and Molecular Insight Pharmaceuticals' Oncology Pipeline

Azedra recognizes this norepinephrine transporter molecular target that is over-expressed in neuroendocrine tumor cells allowing targeted accumulation at these tumor sites. Azedra, developed using Molecular Insight's proprietary Ultratrace™ technology, which permits more efficient and high specific activity labeling with the therapeutically active Iodine-131 isotope, permits maximum delivery of the therapeutic potential of iobenguane I 131, a radiotherapeutic currently marketed in Europe to treat neuroendocrine tumors. At a given therapeutic dose, Azedra -- high specific activity 131 iobenguane -- minimizes the amount of non-radioactive iobenguane molecules administered to the patient, thereby reducing pharmacologic toxicities, especially cardiovascular events or toxicity, and enabling safe, better tolerated and effective treatment.

Azedra is one of two clinical-stage oncology candidates that Molecular Insight is developing for the treatment of neuroendocrine tumors. The Company also is developing Onalta™ (90Y-edotreotide), a radiolabeled somatostatin analog, initially for the treatment of pancreatic neuroendocrine and carcinoid tumors whose symptoms are not controlled by conventional somatostatin analog therapy.

About Molecular Insight Pharmaceuticals, Inc.

Molecular Insight Pharmaceuticals is a clinical-stage biopharmaceutical company and is a pioneer in the emerging field of molecular medicine. The Company is focused on the discovery and development of targeted therapeutic and molecular imaging radiopharmaceuticals, primarily for use in oncology. Molecular Insight has five clinical-stage candidates in development. The lead oncology candidate, Azedra™, is currently in a pivotal trial for pheochromocytoma. Onalta™ is being developed for the treatment of carcinoid and other neuroendocrine tumors, Solazed™ for treatment of malignant metastatic melanoma, and Trofex™ for detecting metastatic prostate cancer. Zemiva™ is being developed for the diagnosis of acute myocardial ischemia. For further information on Molecular Insight Pharmaceuticals, please visit www.molecularinsight.com.

Forward-Looking Statements

Statements in this release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, statements about the potential therapeutic benefit of Azedra, our planned filing of a New Drug Application for Azedra, the timing of FDA review of such application, our corporate strategy, the development of Zemiva™, Trofex™ , Azedra™, Onalta™, Solazed™ and our other product candidates, our programs in pivotal trials and anticipated regulatory requirements,. Such forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause the actual results of Molecular Insight to be materially different from historical results or from any results expressed or implied by such forward-looking statements. These factors include, but are not limited to, risks and uncertainties related to the progress, timing, cost, and results of clinical trials and product development programs; difficulties or delays in obtaining regulatory approval for product candidates; competition from other pharmaceutical or biotechnology companies; and the additional risks discussed in filings with the Securities and Exchange Commission (SEC). The Company's SEC filings are available through the SEC's Electronic Data Gathering Analysis and Retrieval system (EDGAR) at http://www.sec.gov/. Press releases for Molecular Insight Pharmaceuticals, Inc. are available on our website: http://www.molecularinsight.com/. If you would like to receive press releases via e-mail, please contact: investor@molecularinsight.com. All forward-looking statements are qualified in their entirety by this cautionary statement, and Molecular Insight undertakes no obligation to revise or update this release to reflect events or circumstances after the date hereof.

Contact Information