Cabometyx label expansion
On January 16, Exelixis (EXEL) and Ipsen announced positive results from the CELESTIAL Phase 3 trial highlighting the statistically significant and clinically meaningful improvement in the trial’s primary end point of overall survival due to cabozantinib therapy compared to a placebo in second-line and third-line hepatocellular carcinoma (or HCC) patients.
These data formed the basis of the applications submitted by Exelixis and Ipsen to the FDA and the European Medicines Agency (or EMA), respectively, for expanding Cabometyx’s label in the HCC segment.
While the Independent Data Monitoring Committee (or IDMC) stopped the trial during the second interim analysis for efficacy, the trial had been close to rejecting the null hypotheses during the first interim analysis itself. Further, the safety data for cabozantinib from the CELESTIAL trial were consistent with the data seen in previous Cabometyx trials such as METEOR and CABOSUN.
In March 2017, cabozantinib secured an orphan drug designation from the FDA in an HCC indication.
The above diagram shows how cabozantinib is on the way to becoming a preferred vascular endothelial growth factor receptor (or VEGFR) tyrosine-kinase inhibitor (or TKI) in the United States compared to Pfizer’s (PFE) Sutent and Inlyta and Novartis’s (NVS) Votrient.
HCC market opportunity
According to estimated worldwide cancer incidence, mortality, and prevalence statistics released by the International Agency for Research on Cancer in 2012, liver cancer is one of the leading causes of mortality in cancer patients and results in almost 800,000 deaths every year globally.
The American Cancer Society has estimated the annual worldwide incidence of HCC to be close to 800,000, while the incidence of liver cancer patients in the United States is ~40,000. Further, there are ~29,000 deaths attributable to liver cancer in the United States every year.
The Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report estimates that HCC is the third leading cause of mortality in cancer patients across the world. Finally, based on the report, the natural history of HCC, and the prognosis in relation to treatment for 850 patients, the survival rate for HCC without treatment is only six months.
These statistics highlight the scale of market opportunity for cabozantinib in this highly underserved segment. Further, the availability of only one systemic therapy in this indication has increased the need for alternative options in the market.
In the next article, we’ll discuss research programs evaluating cabozantinib-immunotherapy combination regimens in greater detail.