Thyroid, Kidney Cancer Drug Granted Orphan Drug Status for Hepatocellular Carcinoma

Inês Martins, PhD avatar

by Inês Martins, PhD |

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The U.S. Food and Drug Administration has granted orphan drug status to cabozantinib for the treatment of hepatocellular carcinoma, the most common type of liver cancer.

The designation is granted to drugs or treatments meant to treat rare diseases —those affecting fewer than 200,000 people in the U.S. It provides financial incentives, including federal grants, tax credits, and FDA fees to aid in product development. It also grants seven years of marketing exclusivity for the orphan indication.

Cabozantinib is a multi-kinase inhibitor that suppresses the activity of MET, VEGF receptors, AXL, and RET, proteins involved in tumor onset, metastasis, formation of tumor blood vessels, and maintenance of the tumor microenvironment.

It is currently approved under the brand name Cabometrix in a tablet formulation for the treatment of kidney cancer, and as Cometriq (oral capsules) to treat thyroid cancer that has spread to other parts of the body.

Biopharmaceutical company Exelixis is currently conducting a Phase 3 clinical trial to evaluate cabozantinib in patients with advanced hepatocellular carcinoma, who received prior treatment with Nexavar (sorafenib).

The CELESTIAL trial (NCT01908426), a randomized, double-blind, placebo-controlled study, is being conducted at more than 100 cancer centers globally across 19 countries. The study will enroll 760 patients with hepatocellular carcinoma, who will be randomized 2:1 to receive cabozantinib (60 mg) or placebo.

The primary endpoint of the trial is overall survival, and secondary endpoints include objective response rate and progression-free survival. The study also will assess patient-reported outcomes, biomarkers that help determine which patients respond to cabozantinib, and safety of treatment.

In September 2016, an interim analysis from the Phase 3 trial conducted when 50% of the events for overall survival had occurred, the Independent Data Monitoring Committee determined the study should continue without modifications in the protocol.

Based on prior data, researchers are expecting a median overall survival of 8.2 months in the placebo group, and a 32% increase in the median overall survival of cabozantinib-treated patients, at the time of the final analysis. Final results of the trial are expected in 2017.

Hepatocellular carcinoma is the most common type of liver cancer and a leading cause of cancer deaths worldwide. Without treatment, patients have very poor prognosis, usually surviving less than six months after diagnosis.