Eisai Submits Application for Additional Indication of Anticancer Agent Lenvima for Hepatocellular Carcinoma in Japan
2017年6月23日 - 07:34PM
JCN Newswire (英)
Eisai Co., Ltd. announced today that it has submitted an
application for an additional indication of its in-house discovered
and developed anticancer agent Lenvima (generic name: lenvatinib
mesylate) for the treatment of hepatocellular carcinoma (HCC) in
Japan, the first in the world.
This application is based on the results of a multicenter,
open-label, randomized, global Phase III trial (Study 304)
comparing the efficacy and safety of Lenvima versus sorafenib, a
standard treatment for advanced HCC, as a first-line treatment for
954 patients with unresectable HCC.(1)
According to the results of this study, Lenvima met the statistical
criteria for non-inferiority in the primary endpoint of Overall
Survival (OS) compared to sorafenib. Additionally, Lenvima showed
highly statistically significant and clinically meaningful
improvements in the secondary endpoints of Progression Free
Survival (PFS), Time To Progression (TTP), and Objective Response
Rate (ORR), doubling sorafenib's median values and ratios. In this
study, the five most common adverse events observed in the Lenvima
arm were hypertension, diarrhea, decreased appetite, weight loss
and fatigue, which is consistent with the known side-effect profile
of Lenvima. Lenvima is the first agent to meet the statistical
criteria for non-inferiority of OS compared to sorafenib since
sorafenib was approved for the treatment of HCC 10 years ago.
Liver cancer is the second leading cause of cancer related deaths
and is estimated to be responsible for 750,000 deaths per year
globally.(2) Additionally, 780,000 cases are newly diagnosed each
year, about 80% of which occur in 0Asian regions, including Japan
and China.(2) HCC accounts for 85% to 90% of liver cancer cases. It
is estimated that there are approximately 42,000 HCC patients in
Japan,(3) with 26,000 deaths every year.(4) Treatment options for
unresectable HCC are limited and the prognosis is very poor,
meaning that this is an area of high unmet medical needs.
Following the application in Japan, Eisai plans to submit
regulatory applications for Lenvima for the treatment of HCC in the
United States and Europe during the first half of fiscal 2017, and
in China within fiscal 2017.
Lenvima is approved as a treatment for refractory thyroid cancer in
over 50 countries, including the United States, Japan, and in
Europe. Additionally, Lenvima in combination with everolimus is
approved for the treatment of renal cell carcinoma (RCC) in the
United States, and in Europe. In Europe, Lenvima was launched under
the brand name Kisplyx for RCC.
Eisai positions oncology as a key therapeutic area, and is aiming
to discover revolutionary new medicines with the potential to cure
cancer. Eisai is committed to exploring the potential clinical
benefits of Lenvima as it seeks to contribute further to addressing
the diverse needs of, and increasing the benefits provided to,
patients with cancer, their families, and healthcare providers.
About Lenvima (generic name, lenvatinib mesylate)
Discovered and developed in-house, Lenvima is an orally
administered multiple receptor tyrosine kinase (RTK) inhibitor with
a novel binding mode that selectively inhibits the kinase
activities of vascular endothelial growth factor (VEGF) receptors
(VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF)
receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other
proangiogenic and oncogenic pathway-related RTKs (including the
platelet-derived growth factor (PDGF) receptor PDGFRalpha; KIT; and
RET) involved in tumor proliferation. Currently, Eisai has obtained
approval for Lenvima as a treatment for refractory thyroid cancer
in 50 countries, including the United States, Japan, and in Europe.
Additionally, Eisai has obtained approval for the agent in
combination with everolimus in the United States, Europe, and other
countries, as a treatment for renal cell carcinoma (second-line).
In Europe, the agent was launched under the brand name Kisplyx for
RCC. A Phase III study of Lenvima in separate combinations with
everolimus and pembrolizumab in renal cell carcinoma (first-line)
was initiated and is underway. A Phase Ib/II study to investigate
the agent in combination with pembrolizumab in select solid tumors
(non-small cell lung cancer, renal cell carcinoma, endometrial
cancer, urothelial cancer, head and neck cancer, and melanoma) and
a Phase Ib study in hepatocellular carcinoma are underway.
About Study 304(1)
Study 304 is a multicenter, open-label, randomized, global Phase
III study comparing the efficacy and safety of Lenvima versus
sorafenib, a standard treatment for advanced hepatocellular
carcinoma (HCC), as a first-line treatment for patients with
unresectable HCC. In the study, 954 patients were randomized in a
1:1 ratio to receive Lenvima 12 mg (>/=60 kg) or 8 mg (<60
kg) once a day, depending on baseline body weight (n= 478) or
sorafenib 400 mg twice a day (n= 476). Treatment was continued
until disease progression or unacceptable toxicity. The primary
endpoint of the study was Overall Survival (OS), with the goal of
demonstrating non-inferiority. Other factors including Progression
Free Survival (PFS), Time To Progression (TTP), Objective Response
Rate (ORR) and Quality of Life (QOL) were assessed as secondary
endpoints. According to the results of the study, Lenvima (13.6
months) met the statistical criteria for non-inferiority in the
primary endpoint of median OS compared to sorafenib (12.3 months).
(Hazard Ratio [HR] 0.92, 95% Confidence Interval [CI] = 0.79-1.06)
Additionally, Lenvima showed statistically significant improvements
in the three secondary endpoints compared to sorafenib: median PFS
(Lenvima 7.4 months versus sorafenib 3.7 months, HR 0.66, 95% CI =
0.57-0.77, P<0.00001), median TTP (Lenvima 8.9 months versus
sorafenib 3.7 months, HR 0.63, 95% CI = 0.53-0.73, P<0.00001)
and ORR (Lenvima 24% versus sorafenib 9%, P<0.00001).
Furthermore, when overall QOL was evaluated based on the EORTC
QLQ-C30 questionnaire, it was found that Lenvima helped to delay
deterioration of QOL, such as pain and diarrhea, compared to
sorafenib (nominal P-value < 0.05). In this study, the five most
common adverse events observed in the Lenvima arm were
hypertension, diarrhea, decreased appetite, weight loss and
fatigue, which is consistent with the known side-effect profile of
Lenvima.
(1) A. Cheng et al. "Phase 3 trial of lenvatinib vs sorafenib in
first-line treatment of patients with unresectable hepatocellular
carcinoma", the 53rd Annual Meeting of the American Society of
Clinical Oncology (ASCO), (June 2017), Abstract No: 4001
(2) GLOBOCAN2012: Estimated Cancer Incidence, Mortality and
Prevalence Worldwide in 2012. http://globocan.iarc.fr/
(3) Ministry of Health, Labour and Welfare, 2014 Patient Survey
(4) Ministry of Health, Labour and Welfare, 2014 Population Trends
Survey
About Eisai
Eisai Co., Ltd. (TSE:4523; ADR:ESALY) is a research-based human
health care (hhc) company that discovers, develops and markets
products throughout the world. Eisai focuses its efforts in three
therapeutic areas: integrative neuroscience, including neurology
and psychiatric medicines; integrative oncology, which encompasses
oncotherapy and supportive-care treatments; and
vascular/immunological reaction. Through a global network of
research facilities, manufacturing sites and marketing
subsidiaries, Eisai actively participates in all aspects of the
worldwide healthcare system. For more information about Eisai Co.,
Ltd., please visit www.eisai.com.
Source: Eisai
Contact:
Public Relations Department,
Eisai Co., Ltd.
+81-3-3817-5120
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