Eisai Co., Ltd. and Merck announced that the China National Medical Products Administration (NMPA) approved the kinase inhibitor Lenvima (lenvatinib) as a single agent for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy. In China, the application of Lenvima was submitted in October 2017 and was designated for Priority Review by the NMPA due to Lenvima’s significant clinical benefit compared to existing treatments, leading to approval in approximately 10 months. This approval marks the first for Lenvima in China, where the incidence of HCC is high, and the first new systemic therapy approved for the first-line treatment of unresectable HCC in China in ten years.
“Over the past decade, there have been limited treatment options available for patients with unresectable HCC,” said Dr. Takashi Owa, vice president and chief medicine creation officer, Oncology Business Group, Eisai. “We are pleased to be able to deliver Lenvima to HCC patients in China, and we are thankful for the collaborative efforts by regulatory and government authorities, as well as the patients and physicians who participated in the clinical studies and made this approval possible.”
“Today’s milestone for Lenvima is an important one for patients in China living with unresectable HCC, which is historically difficult to treat and has a poor prognosis,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Merck remains committed to bringing new treatment advances to patients in China. The approval of Lenvima, through our collaboration with Eisai, is the third cancer medicine in our portfolio to be approved in China this year—reinforcing the great progress being made to bring new treatment options forward for Chinese patients.”
The approval was based on results from the Reflect study (Study 304), an open-label, Phase 3 trial where Lenvima demonstrated a treatment effect on overall survival (OS) by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC; patients randomized to the Lenvima arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. Lenvima demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR).
In a subpopulation analysis of 288 patients in the study from the greater Chinese region (mainland China, Hong Kong and Taiwan), Lenvima demonstrated efficacy based on non-inferiority of OS compared to sorafenib, with improvements also observed in PFS, TTP and ORR. Approximately 80 percent of patients in the subpopulation were living with HCC resulting from chronic hepatitis B virus (HBV), which has high unmet medical need. For these patients, Lenvima demonstrated non-inferiority based on OS compared with sorafenib, thereby demonstrating the effect of Lenvima in patients with HCC resulting from HBV.
In the China package insert, the five most common adverse reactions observed in patients treated with Lenvima were hypertension (45 percent), fatigue (44 percent), diarrhea (39 percent), decreased appetite (34 percent), and decreased weight (31 percent), which is consistent with the known side-effect profile of Lenvima.
Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for approximately 750,000 deaths per year globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80 percent of which occur in Asian regions. Specifically, in China, there are approximately 395,000 new cases and 380,000 deaths per year, accounting for approximately 50 percent of cases worldwide. HCC accounts for 85 percent to 90 percent of primary liver cancer cases. Unresectable HCC, for which treatment options are limited, is extremely difficult to treat, and the development of new treatments is necessary.
Since the initial launch, more than 10,000 patients have been treated with Lenvima. Lenvima is approved as a treatment for refractory thyroid cancer in over 50 countries including the United States, Japan, in Europe and Asia, and as combination with everolimus as a second-line treatment for renal cell carcinoma (RCC) in over 45 countries including the United States and in Europe. For HCC, Lenvima was approved for use in Japan in March 2018, and in the United States and Europe in August 2018. In Japan, approximately 3,000 HCC patients have been treated with Lenvima since approval of this indication.