Exelixis, Inc. announced that its partner Ipsen has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), for Cabometyx (cabozantinib) 20 mg, 40 mg and 60 mg for the first-line treatment of adults with intermediate- or poor-risk advanced renal cell carcinoma (RCC). The positive CHMP opinion will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union.

“This positive CHMP opinion represents a significant step forward in helping to address an unmet need for patients in Europe with intermediate- or poor-risk advanced RCC, who often fare poorly and are in need of new therapies to better control their disease,” said Michael M. Morrissey, Ph.D., President and chief executive officer of Exelixis. “This is an important milestone in our collaboration with Ipsen as we work together to bring Cabometyx to more patients with advanced kidney cancer and as we continue to study its potential in additional types of cancer.”

Under the terms of the Collaboration and License Agreement with Ipsen, Exelixis is eligible to receive a milestone payment of $50 million for the approval of the first-line treatment of advanced RCC, of which approximately $46 million will be recognized as collaboration revenue in the first quarter 2018. This milestone will be paid by Ipsen within 70 days after notification of the approval decision by the European Commission.

Cabometyx was approved in the European Union in September 2016 for the treatment of advanced RCC in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. The CHMP recommendation to expand the indication is based on results of the CABOSUN trial, which met its primary endpoint of improving progression-free survival (PFS) compared with sunitinib in patients with previously untreated advanced RCC determined to be intermediate- or poor-risk by the International Metastatic RCC Database Consortium (IMDC) criteria. In December 2017, the US Food and Drug Administration (FDA) approved Cabometyx for the expanded indication of patients with advanced RCC based on the results from the CABOSUN trial.

On May 23, 2016, Exelixis announced that the phase 2 CABOSUN study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC as determined by investigator assessment. The CABOSUN study was conducted by The Alliance for Clinical Trials in Oncology and was sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) under the Cooperative Research and Development Agreement with Exelixis for the development of cabozantinib. These results were first presented by Dr. Toni Choueiri at the European Society for Medical Oncology (ESMO) 2016 Congress, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016). In June 2017, a blinded independent radiology review committee (IRC) confirmed that cabozantinib provided a clinically meaningful and statistically significant improvement in the primary efficacy endpoint of investigator-assessed PFS. Results from the IRC review were presented by Dr. Toni Choueiri at the ESMO 2017 Congress.

CABOSUN was a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival, objective response rate and safety. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2 and had to be intermediate- or poor-risk per the IMDC criteria (Heng, JCO, 2009). Prior systemic treatment for RCC was not permitted.

Cabometyx tablets are approved in the United States for the treatment of patients with advanced RCC. Cabometyx tablets are also approved in the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy. Ipsen also submitted to the EMA the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on March 23, 2018, the CHMP provided a positive opinion for Cabometyx for the first-line treatment of intermediate- or poor-risk advanced RCC. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC.

Founded in 1994, Exelixis, Inc. is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers.