Lenvima (Lenvatinib) Receives Regulatory Approvals in Japan, the US, and Europe as a First-Line Treatment for Unresectable Hepatocellular Carcinoma

Eisai and Partner Merck & Co. Announce European Commission Approval of Lenvima (lenvatinib) as First-Line Monotherapy for Advanced or Unresectable Hepatocellular CarcinomaJapanese pharmaceutical company Eisai and its partner Merck & Co. recently jointly announced that the novel targeted anticancer drug Lenvima (lenvatinib) has been approved by the European Commission (EC) as a monotherapy for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC). Lenvima is the first new first-line therapy approved globally in the past decade for advanced or unresectable HCC. Just last week, Lenvima also received approval from the U.S. Food and Drug Administration (FDA) for the same indication. In late March this year, Lenvima was first approved in Japan for the first-line treatment of HCC.

Notably, this EU approval marks the third major market where regulatory clearance has been obtained since Eisai entered into a global strategic collaboration with MSD in March this year to jointly develop and commercialize Lenvima.

This approval is based on data from a Phase III clinical trial (Study 304/REFLECT). This multicenter, randomized, open-label, global clinical study evaluated the efficacy and safety of Lenvima as first-line treatment in patients with unresectable hepatocellular carcinoma (HCC), comparing it with Nexavar (sorafenib), Bayer’s targeted anticancer agent and the standard of care for advanced HCC. In the study, 954 patients were randomized in a 1:1 ratio to receive either Lenvima (12 mg or 8 mg [based on body weight], once daily; n=478) or Nexavar (400 mg, twice daily; n=476) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS), with the objective of demonstrating non-inferiority. Secondary endpoints included progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), patient quality of life, plasma pharmacokinetic (PK) parameters, and safety.

Data show that, compared with Nexavar, Lenvima demonstrated statistically significant non-inferiority in the primary endpoint of overall survival (OS): median OS was 13.6 months in the Lenvima group versus 12.3 months in the Nexavar group (HR=0.92, 95% CI=0.79-1.06). Meanwhile, compared with Nexavar, Lenvima showed highly statistically significant and clinically meaningful improvements in secondary endpoints, including progression-free survival (PFS) (7.4 months vs. 3.7 months; HR=0.66, 95% CI=0.57-0.77, p<0.00001), time to progression (TTP) (8.9 months vs. 3.7 months; HR=0.63, 95% CI=0.53-0.73, p<0.0001), and objective response rate (ORR) (24% vs. 9%, p<0.00001). Furthermore, compared with Nexavar, Lenvima significantly delayed deterioration in several quality of life (QOL) and symptom domains (pre-specified secondary endpoints), including pain and diarrhea (nominal p<0.05).

In terms of safety, the five most common adverse events in the Lenvima treatment group included: hypertension (42%), diarrhea (39%), decreased appetite (34%), weight loss (31%), and fatigue (30%), which is consistent with the known safety profile of Lenvima.

Lenvatinib is an oral multi-receptor tyrosine kinase (RTK) inhibitor with a novel binding mode. In addition to inhibiting other RTKs involved in tumor proliferation, angiogenesis, and oncogenic signaling pathways, it selectively inhibits the kinase activity of vascular endothelial growth factor (VEGF) receptors. To date, lenvatinib has been approved in more than 50 countries worldwide for the treatment of refractory thyroid cancer. It has also received approval in the United States and the European Union for patients with advanced renal cell carcinoma (RCC) who have previously received VEGF-targeted therapy. Furthermore, Eisai is evaluating the potential of lenvatinib for the treatment of various types of tumors.

Current Status of Liver Cancer: China Is a Country with a High Burden of Liver Cancer

Globally, liver cancer is the second leading cause of cancer-related deaths, with 780,000 new cases annually (71,000 new cases per year in Europe) and approximately 750,000 deaths (69,000 per year in Europe). Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer cases. Early-stage HCC can be treated through various modalities, including surgical resection, radiofrequency ablation, percutaneous ethanol injection, and transarterial chemoembolization. However, treatment options for unresectable HCC are very limited, resulting in a poor prognosis and representing a significant unmet medical need. Previously, in clinical practice, Bayer’s targeted anticancer drug Nexavar was the only molecularly targeted agent approved for the first-line treatment of unresectable HCC.

Liver cancer exhibits significant regional disparities, with the majority of cases occurring in Asia, primarily in China, followed by Africa. Hepatocellular carcinoma (HCC) accounts for approximately 85%–90% of primary liver cancers. HCC is associated with chronic liver disease, particularly cirrhosis. The main causes of cirrhosis include hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. However, according to a recent survey, non-HBV/non-HCV-related hepatocellular carcinoma is on the rise.

Original Source: Eisai and Merck Announce European Commission Grants Marketing Authorization for LENVIMA® (lenvatinib) as First-Line Treatment in Adults with Advanced or Unresectable Hepatocellular Carcinoma

Original Title:New Clinical Standard for Liver Cancer! Eisai/MSD’s Lenvima (Lenvatinib) Approved in Japan, the US, and Europe for First-Line Treatment of Unresectable Hepatocellular Carcinoma (HCC)!

Source: Bioon. For more information, please download the Bioon APP (http://www.bioon.com/m/)