AstraZeneca has received Orphan Drug Designation by the US Food and Drug Administration (FDA) for two investigational drug candidates. The Orphan Drug Designation provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US.

The FDA granted Orphan Drug Designation for the company’s anti-CTLA-4 monoclonal antibody, tremelimumab, for the treatment of malignant mesothelioma. Mesothelioma is a rare, aggressive cancer that most often affects the lining of the lungs and abdomen. Available treatments for mesothelioma are very limited, particularly for patients with advanced disease.

Tremelimumab is part of the broad pipeline of immuno-oncology assets being developed by AstraZeneca and its biologics research and development arm, MedImmune, which are designed to harness the body's own immune system to fight cancer. It is a fully human monoclonal antibody, which stimulates the immune system to destroy cancer cells through binding to the protein CTLA-4, expressed on the surface of activated T-lymphocytes. In addition to being investigated as a monotherapy treatment for patients with mesothelioma, tremelimumab is currently being studied in combination with AstraZeneca's anti PD-L1 investigational immunotherapy, MEDI4736, in tumor types including non-small cell lung cancer and head and neck cancer. It is also being studied in combination with Iressa (gefitinib) in EGFR mutated non-small cell lung cancer and with MEDI6469 (a murine OX40 agonist) in solid tumors.

AstraZeneca also was granted Orphan Drug Designation for the MEK inhibitor, selumetinib, for the treatment of uveal melanoma. Uveal melanoma is a rare disease in which cancer cells form in the tissues of the eye. It is the most common primary intraocular malignancy in adults and comprises 5% of all melanomas.

Selumetinib, originally licensed from Array BioPharma Inc., inhibits the MEK pathway in cancer cells to prevent the tumor from growing. Data from a Phase III study evaluating selumetinib in combination with chemotherapy in patients with first-line metastatic uveal melanoma is expected to be available later this year. In addition to uveal melanoma, selumetinib is being investigated in Phase III studies in KRAS-mutation-positive lung cancer and thyroid cancer and in Phase II in children with neurofibromatosis Type 1. Initial data from a combination study of selumetinib with other AstraZeneca pipeline molecules, including AZD9291 (T790M-directed EGFR inhibitor) and MEDI4736 (anti-PD-L1) in non-small cell lung cancer, will be presented at the American Society of Clinical Oncology annual meeting 2015.

Source: AstraZeneca (tremelimumab) and AstraZeneca (selumetinib)