SOURCE: Molecular Insight Pharmaceuticals, Inc.

Molecular Insight Pharmaceuticals, Inc.

June 23, 2010 16:01 ET

Molecular Insight Pharmaceuticals Presents Positive Data From Azedra™ Phase 2a Clinical Trial in Neuroblastoma Tumors

CAMBRIDGE, MA--(Marketwire - June 23, 2010) -  Molecular Insight Pharmaceuticals, Inc. (NASDAQ: MIPI) today presented positive data from a completed Phase 2a clinical study of Azedra™, (Ultratrace™ iobenguane I 131 or Ultratrace I-131-MIBG), the Company's lead oncology therapeutic that targets neuroblastoma, a common childhood cancer. Phase 2a data presented at the Advances in Neuroblastoma Research (ANR) Conference in Stockholm, Sweden, on June 23, 2010, reported that the study successfully provided safety, toxicity and response data. 

Data from the Phase 2a study were presented in an abstract titled A Phase IIa Trial of Ultratrace (no-carrier added) Iobenguane I-131 (MIBG): A New Approaches to Neuroblastoma Therapy (NANT) Study (Abstract 1906390) and in an oral presentation by lead investigator Katherine K. Matthay, M.D., the Mildred V. Strouss Professor of Translational Cancer Research and Chief, Pediatric Hematology-Oncology in Department of Pediatrics at the University of California, San Francisco. Key conclusions from Dr. Matthay's presentation, which included data on an additional seven patients enrolled since the abstract was submitted, include: (a) doses of 12 to 18mCi/kg of Ultratrace iobenguane were tolerated without dose limiting toxicity (DLT); and (b) Ultratrace iobenguane is active in tumors, without significant toxicity, with promising responses as shown by a preliminary observed response rate, using International Neuroblastoma Response Criteria (INRC), in 5 of 13, or 38 percent of currently evaluable patients. The data support proceeding to a pivotal Phase 2 study utilizing the 18 mCi/kg administered therapeutic dose. 

Currently, I-131-MIBG is used to treat neuroblastoma, with a response rate greater than 30 percent in relapsed disease. The presence of non-radioactive "carrier" MIBG molecules may inhibit uptake of I-131-MIBG, resulting in less tumor radiation and increased risk of cardiovascular side effects. Azedra consists of the iobenguane molecule radiolabeled with iodine-131 using the Company's proprietary Ultratrace technology platform, a technique that avoids large quantities of cold (non-radioactive) iobenguane in the formulation of the product. In previous animal studies, the lack of cold iobenguane suggested two significant clinical benefits: greater tumor uptake and reduced pharmacological toxicity or side effects. 

Dr. Matthay noted: "The primary aim of this Phase 2a study was to establish the maximum tolerated dose (MTD) of Ultratrace iobenguane I-131 with autologous hematopoietic stem cell (AHSC) support. We showed that Ultratrace iobenguane I-131 with AHSC support is feasible at 18 mCi/kg without significant toxicity and with promising partial and complete responses that support proceeding to a pivotal Phase 2 study at18 mCi/kg."

The primary objectives of the study were to determine MTD and toxicity graded by Common Terminology Criteria for Adverse Events (CTCAE) of Azedra in patients with refractory high-risk neuroblastoma; estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following a 0.1 mCi/kg intravenous administration of Azedra; and assess objective tumor response following treatment. Secondary objectives include evaluation of objective tumor response by INRC.

Eligible patients were age 1 to 30 years old with resistant neuroblastoma, MIBG uptake, and cryopreserved AHSC. A diagnostic dose of Ultratrace iobenguane (1-5 mCi) was followed by 3 dosimetry scans. The administered therapeutic dose was then adjusted based on absorbed dose estimates and normal organ tolerance limits. AHSC were infused 14 days post therapy. Response and toxicity were evaluated at day 60. The Ultratrace iobenguane was escalated in 3mCi/kg increments from 12-21 mCi/kg using 3+3 design. Dose limiting toxicity was defined as failure to engraft or grade 3 or 4 non-hematologic toxicity except grade 3 pre-defined exclusions. No DLT was observed and there were no related serious adverse events reported. Most commonly reported adverse events (AE) included myelosuppression, gastrointestinal (nausea/vomiting, salivary gland pain/swelling, increased liver function tests, headache and fever. Nearly 80 percent of the reported AEs were Grade 1 and 2 by CTCAE criteria.

About Azedra
Azedra, a novel, targeted radiotherapeutic, recognizes the 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, permits more efficient and high specific activity labeling with the therapeutically active 131-Iodine isotope which could result in 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 minimizes the amount of non-radioactive iobenguane molecules administered to the patient, potentially reducing pharmacologic toxicities, especially cardiovascular events or toxicity, and possibly enabling better tolerated and effective treatment. 

Azedra is currently in advanced clinical trials for the treatment of malignant pheochromocytoma, a rare, hard-to-access neuroendocrine tumor that develops in the core of an adrenal gland. 

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.

A type of NET, neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 new cases per year in the U.S. Neuroblastoma comprises six to ten percent of all childhood cancers, and fifteen percent of cancer deaths in children. Close to 50 percent of neuroblastoma cases occur in children younger than two years old. This type of malignant tumor arises from any neural crest element of the sympathetic nervous system or SNS. Neuroblastoma most frequently originates in one of the patient's adrenal glands, but can also develop in nerve tissues in the neck, chest, abdomen or pelvis.

About Molecular Insight Pharmaceuticals, Inc.
Molecular Insight Pharmaceuticals is a clinical-stage biopharmaceutical company and pioneer in molecular medicine. The Company is focused on the discovery and development of targeted therapeutic and imaging radiopharmaceuticals for use in oncology. Molecular Insight has five clinical-stage candidates in development. 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 in enabling safe, better tolerated and effective treatment, and Azedra's potential proceeding to a pivotal Phase 2 study. 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.

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