Molecular Insight Pharmaceuticals, Inc. Reports Preliminary Results of Azedra Phase I Trial in Neuroendocrine Cancer Patients at ASCOCAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun 2, 2008 - Molecular Insight Pharmaceuticals, Inc. (NASDAQ: MIPI) today announced positive preliminary results from an ongoing Phase 1 clinical study of Azedra (Ultratrace(TM) iobenguane I 131 or Ultratrace MIBG) for the treatment of malignant pheochromocytoma, a type of neuroendocrine cancer. The study, presented during a poster session at the annual meeting of the American Society of Clinical Oncology (ASCO), is the first segment of a Phase 1/2 study that is designed to assess safety and identify Azedra's maximum tolerated dose. A Phase 2/3 portion of the trial, expected to begin in the second half of 2008, will be designed to evaluate Azedra's antitumor efficacy.
Azedra is Molecular Insight's lead targeted radiotherapeutic for cancer that combines the known MIBG molecule with the Company's proprietary Ultratrace technology. MIBG, commercialized in Europe and used on a compassionate basis in the United States, is highly selective for the norepinephrine transporter, a protein overexpressed on neuroendocrine tumors. Molecular Insight's proprietary Ultratrace technology was developed to increase specific activity, enhance tumor uptake and limit dose-related adverse effects without the unnecessary cold contaminants found in current MIBG preparations. The Azedra Phase 1 study is a dose escalation trial that has enrolled 21 patients to date, beginning at a dose of 6.0 mCi/kg. Dosing has currently progressed to 9.0 mCi/kg.
"Preliminary results of this ongoing trial to date are encouraging, as we have been able to continue to raise the therapeutic doses administered to patients, and Ultratrace iobenguane I 131 appears to be safe, well tolerated and provides clinical benefits," said Dr. R. Edward Coleman, Professor of Radiology and Vice Chairman of the Department of Radiology at Duke University Medical Center and Principal Investigator for the trial.
The primary objective of the trial is safety and dose determination. There were 13 of 21 patients with at least three months of antitumor efficacy data available. Preliminary findings of antitumor efficacy to date include 100 percent of patients who were evaluable demonstrating partial response or stable disease at three months (13 of 13 patients), 78 percent at six months (7 of 9 patients) and 67 percent at nine months (2 of 3 patients). Tumor biomarkers, such as serum chromogranin A, 24-hour urine total metanephrines and 24-hour urine vanillylmandelic acid, correlated with reduction in target lesion size. The largest vest overall tumor marker response was seen in Chromogranin A, which was reduced in 73 percent of the patients who were abnormal at baseline. Twenty-five percent of the patients who were on anti-hypertensive medication at baseline (including one patient with a RECIST tumor partial response) reduced their anti-hypertensive medication by 50% or greater within one month after treatment. Additional clinical benefit was observed in most patients, including increased energy levels, decreased pain and/or pain medications and other improvements in quality of life.
"The value of Molecular Insight's Ultratrace technology is being confirmed in the clinical development of Azedra. This dose escalation trial continues to demonstrate that we can deliver therapeutic doses of Azedra that are well tolerated," said John W. Babich, Ph.D., President and Chief Scientific Officer of Molecular Insight. "In particular, no infusion-related cardiovascular effects have been observed in this trial, which may relate to Azedra's ultrapure profile, whereby significantly less cold MIBG is delivered to the patient. We plan to move Azedra into a Phase 2/3 trial once we have established the maximum tolerated dose in this current trial and finalized the next phase of trial design with the FDA."
"This trial furthers Molecular Insight's mission to develop our robust portfolio of targeted radiotherapeutics for the treatment of cancer - in this case, neuroendocrine tumors in adults," said David S. Barlow, Chairman and Chief Executive Officer of Molecular Insight. "We recently initiated an Azedra trial to treat children with neuroblastoma, and we expect to begin a Phase 1 dosimetry trial later this year with Onalta. Onalta is our radiolabeled somatostatin peptide analog product candidate being developed primarily for carcinoid, a neuroendocrine cancer that we believe may complement Azedra's focus on pheochromocytoma and neuroblastoma."
Pheochromocytoma and other neuroendocrine tumors are rare cancers of the nervous and endocrine systems. They generally arise in the adrenal gland, where they typically secrete excess hormones, leading to a variety of clinical syndromes. The five-year survival rate for patients with malignant disease is 50 percent and survival can be 24 months or shorter in patients with progressive, recurrent metastatic disease. There are no approved treatments in the United States for malignant pheochromocytoma and others of these rare tumor types other than surgical resection of the tumor. Patients who are not cured by surgery are usually given palliative care, including surgery to reduce the tumor burden, anti-hypertensive and pain medication. Azedra has been designated as an Orphan Drug with Fast Track status by the U.S. Food and Drug Administration.
The Phase 1 dose escalation trial began at 6.0 mCi/kg and proceeded according to the 3+3 trial design, with dose increases at 1.0 mCi/kg increments. Patients were dosed by weight up to 75 kg (e.g. 6.0 mCi/kg dose cannot exceed 450 mCi). Examples of dose limiting toxicities are febrile neutropenia (temperature (greater than or equal to) 38.5(degree)C and ANC (less than) 1000/(Micro sign)L); Grade 3 thrombocytopenia with active bleeding; Grade 4 hematologic toxicity (greater than)1 week duration; and/or Grade 3-4 non-hematologic toxicity.
Objective tumor and tumor biomarker response were evaluated according to RECIST criteria at 3, 6, 9, and 12 months. In addition, reduction in anti-hypertensive medication, for those patients on anti-hypertensive medication at baseline, was evaluated.
To date three dose limiting toxicities have occurred: one in the second 7.0 mCi/kg cohort (thrombocytopenia and febrile neutropenia), one in the 8.0 mCi/kg dose group (low platelets), and one in the second 9.0 mCi/kg cohort (low absolute neutrophil count). The most common (and expected) adverse events experienced during the study were: anemia, leukopenia, neutropenia, thrombocytopenia, dry mouth, nausea, salivary gland pain, vomiting, fatigue and anorexia. Most were mild or moderate and were self-limited, and none resulted in premature discontinuation from the study.
There were serious adverse events observed in six patients. Among those possibly/probably related to treatment, most were blood/lymphatic system disorders of grade 2 or 3. There was one death due to failure to thrive in a 72-year-old female patient from the 6.0 mCi/kg cohort, whose comorbidities included advanced pre-existing medical conditions. The death was judged by the principal investigator, attending physician and sponsor to be unrelated to the study drug.
About Molecular Insight Pharmaceuticals, Inc.
Molecular Insight Pharmaceuticals (NASDAQ: MIPI) is a biopharmaceutical company specializing in the emerging field of molecular medicine, applying innovations in the identification and targeting of disease at the molecular level to improve healthcare for patients with life-threatening diseases. The company is focused on discovering, developing and commercializing innovative, molecular radiotherapeutics and molecular imaging pharmaceuticals with initial applications in the areas of oncology and cardiology. Its lead molecular radiotherapeutic product candidates, Azedra and Onalta, are being developed for detection and treatment of cancer. The company's lead molecular imaging pharmaceutical product candidate, Zemiva, is being developed for the diagnosis of cardiac ischemia, or insufficient blood flow to the heart. In addition, the company has a growing pipeline of product candidates resulting from application of its proprietary platform technologies to new and existing compounds. Molecular Insight Pharmaceuticals is based in Cambridge, Massachusetts and its website address is: www.molecularinsight.com.
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 development of Azedra(TM), Onalta(TM), Zemiva(TM) and our other product candidates. 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. All forward-looking statements are qualified in their entirety by this cautionary statement, and Molecular Insight undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof.
Molecular Insight Pharmaceuticals, Inc.
Priscilla Harlan, 617-492-5554
Vice President, Corporate Communications
Posted: June 2008