Ipsen Sees First Mover Advantage In EU For Cabometyx In Liver Cancer
Executive Summary
Ipsen CSO says CHMP recommendation for TKI Cabometyx should give it first mover advantage globally in liver cancer.
The likely approval in the EU of Cabometyx in liver cancer would be its third therapy indication after earlier winning first- and second-line treatment status in kidney cancer, giving the tyrosine kinase inhibitor added credibility for its claim to be the TKI of reference globally, Ipsen's chief science officer told Scrip.
It should also result in Cabometyx winning a comfortable lead over upcoming rivals in treating hepatocellular carcinoma (HCC) patients, Alex Lebeaut said in an interview.
HCC To Be Cabometyx's Third EU Indication
He was speaking after news that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), backed Cabometyx (cabozantinib) as a monotherapy for treating liver cancer in adults who have been previously treated with sorafenib.
The panel's positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union, and formal approval is expected in November.
The CHMP recommendation to expand the indication to HCC is based on results from the CELESTIAL trial, a randomized, double-blind, placebo-controlled global Phase III study of Cabometyx versus placebo in patients with advanced HCC who have been previously treated with sorafenib. The study was conducted at more than 100 sites globally in 19 countries.
Datamonitor Healthcare analyst Hardik Patel said the recommendation was indeed important news in HCC, especially given the lack of options available to European patients. The only treatment currently approved for previously treated HCC patients in Europe is Bayer AG's Stivarga (regorafenib).
Ipsen CSO Lebeaut said the French pharma company and its commercial colleagues could use the likely EU approval of Cabometyx in Europe as a beachhead and effective bridge to drive the drug's commercialization.
In 2016, Exelixis Inc. granted Ipsen exclusive rights for the commercialization and further clinical development of Cabometyx outside the US and Japan. Exelixis markets Cabometyx in the US while Takeda Pharmaceutical Co. Ltd. has the rights for Japan.
Cabometyx is an oral therapy that works on a number of targets, including VEGFR2, MET and RET. It has not yet been approved in the US for HCC. The FDA has given it a decision action date of Jan. 14, 2019.
The drug was approved by the US FDA in 2013 for treating the very rare medullary thyroid cancer. Labeling was expanded in April 2016 to second-line renal cell carcinoma (RCC) and in December 2017 to all lines of advanced RCC.
In the European Union, Norway, Iceland, Australia, Switzerland and South Korea it is approved for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy and for previously untreated intermediate- or poor-risk advanced RCC.
Competitive Landscape
Key competitors to the TKI are Bristol-Myers Squibb Co.'s PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab). These will eventually pose a significant threat to Cabometyx, Patel told Scrip.
But the duo's regulatory filings in the US were based on results of early-phase trials which likely aren’t robust enough to support European approval. Indeed, in July 2017 BMS withdrew its application for a change to the European marketing authorisation for Opdivo to include the treatment of liver cancer. Therefore, Ipsen will look to maximize Cabometyx’s EU market share before these competitors gain approval, CSO Lebeaut told Scrip.
Datamonitor Healthcare's Patel said the CELESTIAL study had shown impressive efficacy from Cabometyx in HCC.
"The Phase III RESORCE trial in patients previously treated with Nexavar showed that the addition of Stivarga to best supportive care granted patients with a 2.8-month increase in overall survival in comparison to best supportive care alone. On the other hand, in the Phase III CELESTIAL trial, patients previously treated with Nexavar who received Cabometyx saw a 4.1-month benefit in terms of overall survival versus patients who received placebo. Based on the clinical evidence and the current need for further treatment options, Cabometyx should be able to gain significant uptake in previously treated patients," Patel said.
Lebeaut said Cabometyx's credibility had been much improved earlier this month by updated National Comprehensive Cancer Network (NCCN) clinical practice guidelines which highlighted it as a preferred treatment option. (Also see "Exelixis: NCCN Change Supports Broader Use Of Cabometyx In Kidney Cancer" - Scrip, 8 Sep, 2018.)
He said the expected additional indication in HCC would strongly enhance the drug's attractiveness to patients and physicians.
"Based on this expected third indication in liver cancer and following its approval in RCC, and in light of the recently updated clinical practice guidelines from NCCN, we strongly believe that Cabometyx will become the TKI of reference worldwide.
"We in future will see Cabometyx used as a monotherapy and also more and more in combination with checkpoint inhibitors." Among various ongoing combination studies of the drug in RCC are a Phase II study with BMS's PD-1 inhibitor Opdivo, a Phase I/II study in combination with Keytruda (Merck & Co's PD-1 inhibitor pembrolizumab) and a Phase Ib study in combination with Merck KGaA's PD-L1 inhibitor avelumab.
European Sales Projections
In an exclusive interview in April, Ipsen CFO Aymeric Le Chatelier said he saw Cabometyx generating peak sales in Europe of €300m in treating RCC, either in first-line, second-line or even later in third-line treatment positioning for renal cell cancer and an additional €100m for treating HCC.