Eisai and Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that the European Commission (EC) has granted a marketing authorization for the oral receptor tyrosine kinase (RTK) inhibitor LENVIMA® (lenvatinib), as a single agent for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy. Treatment options for this type of liver cancer are limited, and the prognosis is poor.LENVIMA is the first new, first-line treatment for advanced or unresectable HCC in a decade to show an overall survival (OS) treatment effect by statistical confirmation of non-inferiority against standard of care.
Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for nearly 750,000 deaths per year globally (69,000 per year in Europe), with over 780,000 cases newly diagnosed each year (71,000 per year in Europe). Hepatocellular carcinoma represents about 90 percent of primary liver cancer cases and due to the underlying nature of the disease, surgery is generally not an option.
“Patients with hepatocellular carcinoma are faced with a cancer that is difficult to treat and has a particularly poor prognosis, with only one systemic first-line treatment option currently available,” said Gary Hendler, Chairman and CEO, Eisai EMEA. “LENVIMA is the first new treatment option to be made available in this first-line systemic treatment setting in over a decade and represents an important new therapeutic option for patients. Eisai and Merck are therefore committed to working together to ensure that patients have rapid access to LENVIMA across Europe.”
“Today’s approval brings an important new first-line treatment option to patients with hepatocellular carcinoma in Europe,” said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “As a result of our efforts with Eisai on LENVIMA, we continue to make significant progress in gaining regulatory approval in countries around the world, as we strive together to make this medicine available to patients in need as quickly as possible.”
This approval was based on results from REFLECT (Study 304), an open-label, Phase 3 trial where LENVIMA demonstrated a treatment effect on OS by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC. LENVIMA also demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS) and objective response rate (ORR).
Currently, LENVIMA is marketed in Japan for the treatment of HCC and in the United States for the treatment of first-line unresectable HCC, and applications seeking approval for this indication have been submitted to additional countries.
About the REFLECT Trial (Study 304)
REFLECT was a large (n=954), Phase 3, randomized, multi-center, open-label trial conducted by Eisai to compare the efficacy and safety of LENVIMA versus sorafenib as a first-line systemic treatment in patients with unresectable HCC. Patients at 154 trial sites in 20 countries were randomized to receive LENVIMA 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was OS, tested first for non-inferiority to sorafenib, then for superiority. The key secondary efficacy endpoints of this study included PFS, time to progression (TTP) and ORR, tested for superiority to sorafenib.
REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (HR: 0.92; 95% CI: 0.79–1.06). The OS analysis was conducted as prespecified in the statistical analysis plan when 351 events had occurred in the LENVIMA arm and 350 events had occurred in the sorafenib arm. Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS and ORR, as confirmed by a blinded independent imaging review (IIR):