Date: 2014-03-25
Type of information: Granting of a Market Authorisation in the EU
Product name: Cometriq®
Compound: cabozantinib
Therapeutic area: Cancer - Oncology
Action mechanism:
- tyrosine kinase inhibitor. Cometriq® is a kinase inhibitor that blocks abnormal kinase proteins involved in the development and growth of medullary cancer cells. Patients should not eat for at least 2 hours before and 1 hour after taking Cometriq®.
The active substance of Cometriq® is cabozantinib, an antineoplastic agent, protein kinase inhibitor. Cabozantinib inhibits multiple receptor tyrosine kinases (RTKs) implicated in tumour growth and angiogenesis, pathologic bone remodeling, and metastatic progression of cancer. By inhibiting RTKs, cabozantinib may slow or stop the growth of medullary thyroid cancer.
Company: Exelixis (USA)
Disease: metastasized medullary thyroid cancer
Latest news:
- • On March 25, 2014, Swedish Orphan Biovitrum and Exelixis have announced that the European Commission has approved Cometriq® (cabozantinib) for the treatment of adult patients with progressive, unresectable locally advanced or metastatic medullary thyroid carcinoma (MTC). The European Commission granted conditional marketing authorisation following a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) issued in December 2013. Similar to another drug approved in this setting, the approved indication states that for patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions.The Committee for Orphan Medicinal Products (COMP) also reviewed the designation for Cometriq (cabozantinib) as an orphan medicinal product for the treatment of MTC, and recommended maintenance of orphan drug designation at the time of marketing authorisation.
The FDA approved Cometriq® for the treatment of progressive, metastatic MTC in the United States on November 29, 2012. The approvals of Cometriq® in both the United States and the European Union were based on data from EXAM, the international, multi-centre, randomised double-blinded controlled phase 3 clinical trial conducted in 330 patients with progressive, unresectable locally advanced or metastatic MTC, in which cabozantinib met its primary efficacy endpoint of improving progression-free survival (PFS) as compared to placebo. Pursuant to the terms of a commercialization and distribution agreement between Exelixis and Sobi signed in February 2013, Sobi will support the commercialisation of Cometriq in the European Union for the approved indication through the end of 2015.
• On December 19, 2013, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the granting of a conditional marketing authorisation for Cometriq® 20 mg and 80 mg hard capsules, intended for the treatment of medullary thyroid cancer, that cannot be removed by surgery or that has spread to other parts of the body. For patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decision. Cometriq® was designated as an orphan medicinal product on 26 February 2009. The MAA upon which the CHMP issued its opinion contains data from EXAM, the international, multi-center, randomized double-blinded controlled phase 3 clinical trial conducted in 330 patients with progressive, unresectable locally advanced or metastatic medullary thyroid cancer, in which cabozantinib met its primary efficacy endpoint of improving progression-free survival (PFS) as compared to placebo.
If the European Commission approves Cometriq® based on the CHMP’s positive opinion, Swedish Orphan Biovitrum (Sobi) would support the product’s commercialization in the European Union for the approved indication through the end of 2015, pursuant to the terms of a commercialization and distribution agreement between Exelixis and Sobi signed in January 2013.
• On January 24, 2013, Exelixis has announced the commercial availability of Cometriq® (cabozantinib) for the treatment of patients with progressive, metastatic medullary thyroid cancer. The FDA approved Cometriq® on November 29, 2012. It is being distributed exclusively through Diplomat Specialty Pharmacy in the U.S.
•On November 29, 2012, the FDA has approved Cometriq® (cabozantinib) to treat metastasized medullary thyroid cancer. The FDA completed review of Cometriq®’s application in six months under the agency’s priority review program. This program provides for an expedited six-month review for drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists. Cometriq® also received orphan-product designation by the FDA because it is intended to treat a rare disease or condition. The safety and effectiveness of Cometriq® were established in a clinical study involving 330 patients with medullary thyroid cancer. Treatment with Cometriq® increased the length of time a patient lived without the cancer progressing (progression-free survival) and, in some patients, reduced the size of tumors (response rate). Patients who were given Cometriq® lived an average of 11.2 months without tumor growth compared with an average of four months in patients receiving a sugar pill (placebo). Results also showed that 27 percent of patients treated with Cometriq® had reductions in tumor size lasting an average of nearly 15 months, while patients who received a placebo saw no reductions. Treatment with Cometriq® did not extend patients’ lives. The prescribing information for Cometriq® includes a Boxed Warning alerting patients and health care professionals that severe and fatal bleeding and holes (perforations and fistula) in the colon occurred in some patients.
The most common side effects were diarrhea; inflammation or sores of the mouth; redness, pain, or swelling of the digits (hand-foot syndrome); weight loss; loss of appetite; nausea; fatigue; oral pain; graying or loss of hair color; bad taste; new or worsening high blood pressure; abdominal pain and constipation. The most common laboratory abnormalities included increases in liver enzymes, low calcium and phosphorus, decreased white blood cells and platelets.
• On November 29, 2012, Exelixis has also announced that 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 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 FDA.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2012-11-29
UE authorization: 2014-03-24
Favourable opinion UE: 2013-12-19
Favourable opinion USA:
Orphan status USA: 2010-11-29
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
