Eisai's New Drug Application of Anticancer Agent Lenvatinib for Hepatocellular Carcinoma Accepted in China
2017年10月31日 - 1:05PM
JCN Newswire (英)
Eisai Co., Ltd. announced that the China Food and Drug
Administration (CFDA) has accepted for review a New Drug
Application (NDA) submitted for Eisai's in-house discovered and
developed anticancer agent lenvatinib mesylate (product names:
Lenvima / Kisplyx, "lenvatinib") for use in the treatment of
hepatocellular carcinoma (HCC) in China.
The NDA was based on the results of the REFLECT study (Study 304),
a multicenter, open-label, randomized, global Phase III trial
comparing the efficacy and safety of lenvatinib versus sorafenib, a
standard treatment for HCC, as a first-line treatment for the
patients with unresectable HCC.(1)
In the REFLECT study, lenvatinib demonstrated a treatment effect on
the primary endpoint of Overall Survival (OS) by the statistical
confirmation of non-inferiority to sorafenib. Additionally,
lenvatinib showed highly statistically significant and clinically
meaningful improvements compared to sorafenib in the secondary
endpoints of Progression Free Survival (PFS), Time To Progression
(TTP), and Objective Response Rate (ORR). In this study, the five
most common adverse events observed in the lenvatinib arm were
hypertension, diarrhea, decreased appetite, weight loss and
fatigue, which is consistent with the known side-effect profile of
lenvatinib.
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% 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% of cases worldwide.2 HCC accounts for 85% to 90% of primary
liver cancer cases. Treatment options for unresectable HCC are
limited. Therefore, HCC is extremely difficult to treat, and the
development of new treatments is necessary.
Eisai submitted applications for an additional indication for
lenvatinib for the treatment of HCC in Japan (June 2017), the
United States and Europe (July 2017).
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 lenvatinib 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 lenvatinib mesylate (generic name, "lenvatinib", product
name: Lenvima / Kisplyx)
Discovered and developed in-house, lenvatinib 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 lenvatinib as a treatment for refractory thyroid
cancer in over 50 countries, including the United States, Japan,
and in Europe, under the brand name Lenvima. Additionally, Eisai
has obtained approval for the agent in combination with everolimus
as a treatment for renal cell carcinoma (second-line) in over 40
countries, including the United States and in Europe. In Europe,
the agent was launched under the brand name Kisplyx for renal cell
carcinoma. A Phase III study of lenvatinib in separate combinations
with everolimus and pembrolizumab in renal cell carcinoma
(first-line) is underway. A Phase Ib/II study to investigate the
agent in combination with pembrolizumab in select solid tumors
(endometrial cancer, non-small cell lung cancer, renal cell
carcinoma, urothelial cancer, head and neck cancer, and melanoma)
and a Phase Ib study in HCC are also underway. Additionally, a
Phase Ib study to investigate the agent in combination with
nivolumab in HCC are initiated in Japan.
About the RELECT study (Study 304)(1)
The REFLECT is a multicenter, open-label, randomized, global Phase
III study comparing the efficacy and safety of lenvatinib versus
sorafenib. In the study, 954 patients were randomized in a 1:1
ratio to receive lenvatinib 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 OS with the goal of demonstrating non-inferiority. Other
factors including PFS, TTP, ORR and Quality of Life (QOL) were
assessed as secondary endpoints. According to the results of the
study, lenvatinib (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, lenvatinib showed
statistically significant improvements in the three secondary
efficacy endpoints, doubling sorafenib's median values and ratios:
median PFS (lenvatinib 7.4 months versus sorafenib 3.7 months, HR
0.66, 95% CI = 0.57-0.77, P<0.00001), median TTP (lenvatinib 8.9
months versus sorafenib 3.7 months, HR 0.63, 95% CI = 0.53-0.73,
P<0.00001) and ORR (lenvatinib 24% versus sorafenib 9%,
P<0.00001). Furthermore, EORTC QLQ-C30 and QLQ-HCC18
questionnaires were used to evaluate overall QOL. In both groups,
scores decreased after the administration of the agents. However,
within 3 categories in EORTC QLQ-C30 (role functioning, pain,
diarrhea) and two categories in QLQ-HCC18 (nutrition, body image),
it was found that Lenvatinib helped to delay deterioration of QOL
compared to sorafenib (nominal P-value < 0.01) In this study,
the five most common adverse events observed in the lenvatinib arm
were hypertension, diarrhea, decreased appetite, weight loss and
fatigue, which is consistent with the known side-effect profile of
lenvatinib.
(1) Cheng A 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/
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
Copyright 2017 JCN Newswire . All rights reserved.