Exelixis, Inc. (NASDAQ: EXEL) today announced the European Medicines Agency (EMA) has accepted for review the Marketing Authorization Application (MAA) for COMETRIQ™ (cabozantinib) for the proposed indication of treatment of progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). The completion of the MAA validation process confirms that the submission is sufficient to permit a substantive review for marketing authorization in the European Union.
The MAA contains data from EXAM, the phase 3 pivotal study of COMETRIQ in progressive, metastatic MTC. This trial also served as the basis for Exelixis’ New Drug Application with the U.S. Food and Drug Administration (FDA). The FDA approved COMETRIQ for the treatment of progressive, metastatic MTC on November 29, 2012.
COMETRIQ (cabozantinib) received orphan drug designation in the European Union from the Committee for Orphan Medicinal Products (COMP) for the treatment of MTC.
COMETRIQ (cabozantinib) inhibits the activity of tyrosine kinases including RET, MET and VEGFR2. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.
Exelixis received approval by the FDA to market COMETRIQ in the United States for the treatment of progressive, metastatic MTC in November 2012. Please see important safety information below, and the full prescribing information, including Boxed Warning, for COMETRIQ at
COMETRIQ™ Important Safety Information, including Boxed Warning
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
- Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQ-treated patients.
- Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.
- COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.
- Wound complications have been reported with COMETRIQ.
- COMETRIQ treatment results in an increase in hypertension.
- Osteonecrosis of the jaw has been observed in COMETRIQ-treated patients.
- Palmar-Plantar Erythrodysesthesia (PPE) Syndrome occurs in patients treated with COMETRIQ.
- The kidneys can be adversely affected by COMETRIQ. Proteinuria and nephrotic syndrome have been reported in patients receiving COMETRIQ.
- Reversible Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ.
- COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.