Exelixis, Inc.,  a commercially successful, oncology-focused biotechnology company, has completed the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for Cabometyx (cabozantinib) tablets as a treatment for patients with previously treated advanced hepatocellular carcinoma (HCC).

The sNDA submission is based on results from the CELESTIAL randomized pivotal phase 3 trial of Cabometyx in patients with advanced HCC who received prior sorafenib.

“We look forward to working closely with regulatory authorities through the review process in anticipation of bringing Cabometyx to people diagnosed with advanced hepatocellular carcinoma, an underserved patient community that urgently needs new treatment options,” said Gisela Schwab, M.D., president, product development and medical affairs and chief medical officer, Exelixis. "We would sincerely like to thank the study patients and clinicians who participated in the CELESTIAL trial as well as our dedicated clinical development, medical and regulatory teams for bringing us another step closer to our goal of fully exploring the potential of Cabometyx and making it accessible to every patient who may benefit from its use.”

On October 16, 2017, Exelixis announced that the independent data monitoring committee for the study recommended that the CELESTIAL trial be stopped for efficacy following review at the second planned interim analysis, with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with previously treated advanced HCC (pre-specified critical p-value = 0.021). In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC.

An sNDA is an application to the FDA that, if approved, will allow a drug sponsor to make changes to a previously approved product label, including modifications to the indication.

CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

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 vascular endothelial growth factor (VEGF)-targeted therapy. Ipsen also submitted to European Medicines Agency (EMA) the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on September 8, 2017, Ipsen announced that the EMA validated the application. 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.