Ipsen will commercialize and further co-develop Elelixis’ lead cancer drug cabozantinib under an exclusive licensing agreement that could generate up to $855 million-plus for Exelixis, the companies said today.
The deal gives Ipsen exclusive commercialization rights to current and future indications for cabozantinib outside the U.S., Canada, and Japan. Cabozantinib is a small-molecule inhibitor of tyrosine kinases, including the vascular endothelial growth factor (VEGF) receptors MET, AXL, and RET.
According to the companies, future commercial indications for cabozantinib could include advanced hepatocellular carcinoma (HCC), the subject of the Exelixis-sponsored CELESTIAL Phase III trial, for which topline results are anticipated next year.
Additional earlier-stage studies for cabozantinib are under way through Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP) and its ongoing Investigator-Sponsored Trial (IST) program. Through these programs, the cancer compound is being assessed in more than 45 ongoing or planned studies—including trials in advanced renal cell carcinoma (RCC), bladder cancer, colorectal cancer, non-small cell lung cancer, and endometrial cancer.
“This transaction will help Ipsen accelerate the growth of the company and strengthen its oncology footprint in Europe,” Ipsen Chairman and CEO Marc de Garidel said in a statement. “The robust results from the METEOR study in advanced renal cell carcinoma demonstrate that cabozantinib has the potential to become a key oncology product in Europe.”
METEOR is a Phase III trial that compares a tablet form of cabozantinib to the standard-of-care therapy everolimus in 658 patients with advanced RCC whose disease progressed following treatment with a VEGF receptor (VEGFR) tyrosine kinase inhibitor (TKI).
According to data published in The New England Journal of Medicine, cabozantinib met its primary progression-free survival endpoint, with a median progression-free survival (PFS) of 7.4 months versus 3.8 months for everolimus. The cancer treatment also met its secondary overall response rate endpoint, showing a 42% reduction in the rate of disease progression or death compared with everolimus.
After a preplanned interim analysis showing a strong overall survival trend for cabozantinib did not reach statistical significance, Exelixis said it undertook a second interim analysis that demonstrated a “highly statistically significant and clinically meaningful” increase in overall survival (OS) for cabozantinib. The company says that data has been shared with regulators, and will be presented later this year at a medical conference.
Based on METEOR results, the tablet form of cabozantinib is the subject of applications pending in the U.S. In Europe, Exelixis’ marketing authorization application (MAA) has been granted 150-day “accelerated” assessment, versus the standard 210 days. Exelixis said it plans to transfer sponsorship of the MAA to Ipsen.
Exelixis will maintain exclusive commercial rights for the cancer candidate in the U.S. and Canada and will continue talks toward finding a partner for Japanese commercial rights.
“While our immediate priority will be on advanced renal cell carcinoma, Exelixis and Ipsen are committed to exploring and potentially developing cabozantinib in a variety of cancer settings,” added Exelixis President and CEO Michael M. Morrissey, Ph.D.
In 2014, Exelixis eliminated about 70% of its workforce—160 jobs—following the failure of cabozantinib in a Phase III study comparing the drug to prednisone in men with metastatic castration-resistant prostate cancer.
Now, Exelixis will receive $200 million upfront from Ipsen and will be eligible for payments tied to regulatory milestones, including $60 million upon approval of cabozantinib in Europe for advanced RCC, $50 million upon the filing and approval of cabozantinib in Europe for advanced HCC, plus additional regulatory milestones for potential further indications.
The agreement also includes up to $545 million of potential commercial milestone payments and enables Exelixis to receive tiered royalties up to 26% on Ipsen’s net sales of cabozantinib in its territories.
The agreement also includes rights to the marketed capsule form of cabozantinib, COMETRIQ®, approved in the U.S. in 2012 for progressive, metastatic medullary thyroid cancer (MTC). Two years later, COMETRIQ won E.U. approval in adults with progressive, unresectable, locally advanced or metastatic MTC.
Exelixis said it anticipates shifting ex-U.S. COMETRIQ commercialization rights to Ipsen from its current international partner, Swedish Orphan Biovitrum (Sobi).