Molecular Insight Pharmaceuticals, Inc has initiated a pivotal phase-2 clinical trial for Azedra (Ultratrace Iobenguane I 131), its lead oncology candidate for the treatment of malignant pheochromocytoma, a type of neuroendocrine cancer. The single-arm trial will evaluate the efficacy and safety of Azedra in adult patients with malignant relapsed/refractory pheochromocytoma and position Molecular Insight to file a New Drug Application (NDA).

Azedra has been designated as an Orphan Drug with Fast Track status by the US Food and Drug Administration.

Pheochromocytoma tumours are usually found in the adrenal glands, but may arise in other areas of the body. For malignant pheochromocytoma, radiation therapy offers short-term symptomatic relief, but no cure. Chemotherapy trials have failed to produce cures or significant remissions. For patients with this malignant disease, for whom surgery is not an option, the five-year survival rate is less than 50 per cent.

Azedra is a targeted radiotherapeutic, which consists of the known iobenguane I 131 molecule (commonly known as I-131-MIBG) radiolabeled using the company's proprietary Ultratrace technology. If successful, Azedra would be the first anti-cancer therapy in the United States indicated for the treatment of pheochromocytoma. Molecular Insight also is developing Azedra for the treatment of neuroblastoma, a type of neuroendocrine cancer in children.

Daniel L Peters, president and chief executive officer of Molecular Insight, said, "The launch of this trial marks a significant milestone for our Azedra programme, which addresses the clear need for new treatment options for pheochromocytoma. Azedra is a promising candidate. This targeted radiotherapeutic demonstrated high tumour uptake in preclinical studies and favourable pharmacokinetics in completed trials. Azedra's development underscores Molecular Insight's commitment to apply innovative approaches to address unmet patient needs."

In March 2009, Molecular Insight received Special Protocal Assessment approval from the US Federal Drug Administration (FDA) for the phase-2 trial. Azedra trial IB-12B will be conducted in 58 adults (evaluable) with pheochromocytoma with an expected enrollment of about 75.

Pheochromocytoma tumours cause excess release of the hormones epinephrine and norepinephrine, producing adverse and often severe effects on a patient's heart rate and blood pressure. The primary endpoint of the study will be Azedra's ability to reduce the need for anti-hypertensive medications required to treat the elevated blood pressure often seen as a key sign of the cancer. This trial has begun at centers in the United States and ultimately will include sites in Western Europe.

John W Babich, Molecular Insight's executive vice president, chief scientific officer and president of Research and Development, said, "Molecular Insight is combining an already commercialized molecule with our proprietary Ultratrace radiolabeling technology. We believe that the Ultratrace technology platform enables us to maximize the therapeutic value of Azedra by eliminating unnecessary cold contaminants, or non-radioactive iobenguane, which provide no therapeutic benefit. The absence of cold contaminants allows greater tumour concentration of Azedra and reduced side effects related to the drug's administration."

Molecular Insight also announced that it has contracted with MDS Nordion, Ottawa, Ontario, Canada, to manufacture and supply Azedra for late-stage clinical trials and, upon FDA approval, for commercial use.

Azedra recognizes a unique molecular target over-expressed on the surface of certain neuroendocrine cancer cells, which enables the drug to be accumulated selectively by the tumour.