Exelixis, Inc. announced that the US Food & Drug Administration (FDA) has granted orphan drug designation to XL184 for treatment of follicular, medullary, and anaplastic thyroid carcinoma, and metastatic or locally advanced papillary thyroid cancer. A pivotal phase 3 trial of XL184 is ongoing in patients with Medullary Thyroid Cancer (MTC) and the company expects to release top-line phase III results in the first-half of 2011 and potentially file a New Drug Application (NDA) for the compound in the second-half of 2011.

Exelixis also is evaluating XL184 in phase II in solid tumours including metastatic castration-resistant prostate cancer, ovarian cancer, melanoma, breast cancer, non-small cell lung cancer, and hepatocellular cancer, and in a phase 1 trial in renal cell carcinoma and differentiated thyroid cancer. Additionally, a phase II trial in recurrent glioblastoma is ongoing.

Orphan drug status is granted to treatments for diseases that affect fewer than 200,000 people in the US and provides the benefits of extended market exclusivity for seven years, tax credits of up to 50% of the qualified clinical trial expenses and a waiver of FDA user fees.

“We are looking forward to advancing XL184 as a new potential treatment for MTC, for which we expect to file an NDA in the second half of 2011. This will be an important step toward advancing the care of patients with this cancer,” said Michael M. Morrissey, PhD, president and chief executive officer of Exelixis. “We intend to leverage the benefits associated with orphan drug status to support our aggressive development of XL184 in a broad number of cancers. We believe this will help position us towards achieving our goals of improving outcomes for patients in some of the largest cancer indications while realizing the commercial potential of this first-in-class dual MET/VEGFR inhibitor.”

Exelixis also announced that the United States Adopted Name Council (USANC) and the World Health Organization's INN programme have adopted cabozantinib as the generic name for XL184. The USANC is tri-sponsored by the American Medical Association (AMA), the United States Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA), and establishes drug nomenclature classifications based on pharmacological and/or chemical relationships.

Cabozantinib, an inhibitor of tumour growth, metastasis, and angiogenesis, simultaneously targets MET and VEGFR2, key kinases involved in the development and progression of many cancers. It has recently been shown in preclinical models that treatment with selective inhibitors of VEGF signalling can result in tumours that are more invasive and aggressive compared to control treatment. In preclinical studies, up-regulation of MET has been shown to occur in concert with development of invasiveness after selective anti-VEGF therapy, and may constitute a mechanism of acquired or evasive resistance to agents that target VEGF signalling without inhibiting MET. Accordingly, treatment with cabozantinib in similar preclinical studies resulted in tumours that were less invasive and aggressive compared to control or selective anti-VEGF treatment. Therefore, cabozantinib has the potential for improving outcomes in a range of indications, including those where selective anti-VEGF therapy has shown minimal or no activity.

Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer. The company is leveraging its biological expertise and integrated research and development capabilities to generate a pipeline of development compounds with significant therapeutic and commercial potential for the treatment of cancer.