HATFIELD, England, December 16, 2015 /PRNewswire/ --
FOR EUROPEAN MEDIA ONLY - NOT FOR AUSTRIAN/SWISS JOURNALISTS
New treatment option for advanced thyroid cancer, Lenvima® (lenvatinib) has been approved for reimbursement by the Dental and Pharmaceutical Benefits Agency (TLV) in Sweden.
In May 2015, lenvatinib was approved by the EMA (European Medicines Agency) for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).
While thyroid cancer is relatively rare, over the past few decades the incidence of the disease is rising rapidly across the whole of Europe., In 2012 there were approximately 1,300 new cases of thyroid cancer in Nordic countries. More prevalent in women than men, at a ratio of 2 to 1, thyroid cancer is the most common endocrine malignancy.
Lenvatinib, discovered and developed by Eisai, is an oral molecular tri-specific targeted therapy that possesses a potent selectivity and a binding mode different to other tyrosine kinase inhibitors (TKI). Lenvatinib simultaneously inhibits the activities of several different molecules including vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), RET, KIT and platelet-derived growth factor receptors (PDGFR). This potentially makes lenvatinib the first TKI that simultaneously inhibits the kinase activities of FGFR 1-4 as well as VEGFR 1-3., In addition, lenvatinib was found to have a new Type V binding mode of kinase inhibition that is distinct from existing compounds.,
The reimbursement was based on the SELECT trial which is a randomised, double-blind, multicentre trial for people with progressive RAI DTC (n=392). Lenvatinib shows a significant median 18.3 months progression free survival versus 3.6 months for placebo (hazard ratio [HR] 0.21; 99% confidence interval 0.14-0.31, p<0.0001). The response rate was 64.8% in the lenvatinib group (4 complete responses, 1.5%) and 1.5% in the placebo (p<0.001). 70.4% of patients had a complete or partial response to lenvatinib within 30 days on the 24mg dose. Lenvatinib was associated with a median time to objective response of 2 months (95% CI, 1.9-3.5). Median duration of treatment was 13.8 months with lenvatinib versus 3.9 months for placebo. For lenvatinib, the most common treatment related adverse events were hypertension, diarrhoea, fatigue, decreased appetite, decreased weight, and nausea.
Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, Europe, Switzerland and Japan, and has been submitted for regulatory approval in South Korea, Canada, Singapore, Russia, Australia and Brazil. Lenvima was granted Orphan Drug Designation in Japan for thyroid cancer, in the United States for treatment of follicular, medullary, anaplastic, and metastatic or locally advanced papillary thyroid cancer and in Europe for follicular and papillary thyroid cancer.
The development of lenvatinib underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and well-being of people worldwide. Eisai is committed to the therapeutic area of oncology and to address the unmet medical needs of patients and their families.
Notes to Editors
About Lenvatinib's Novel Binding Mode (Type V),
Kinase inhibitors are categorized into several types (Type I to Type V) depending on the binding site and the conformation of the targeted kinase in complex with them. Most of the currently approved tyrosine kinase inhibitors are either Type I or Type II, however according to X-ray crystal structural analysis, lenvatinib was found to possess a new Type V binding mode of kinase inhibition that is distinct from existing compounds. In addition, lenvatinib was confirmed via kinetic analysis to exhibit rapid and potent inhibition of kinase activity, and it is suggested that this may be attributed to its novel binding mode.
The SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) study was a multicentre, randomised, double-blind, placebo-controlled Phase III study to compare the PFS of patients with RR- radioiodine-refractory differentiated thyroid cancer and radiographic evidence of disease progression within the prior 13 months, treated with once-daily, oral lenvatinib (24mg) versus placebo. The study enrolled 392 patients in over 100 sites in Europe, North and South America and Asia and was conducted by Eisai in collaboration with the SFJ Pharmaceuticals Group.
Participants were stratified by age (≤65, >65 years), region and ≤1 prior VEGFR-targeted therapies and randomised 2:1 to either lenvatinib or placebo therapy (24mg/d, 28-d cycle). The primary endpoint was PFS assessed by independent radiologic review. The secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety. Rates of complete response were 1.5% (4 patients) for the lenvatinib group and zero in the placebo group. The results for partial response were 63.2% (165 patients) in the lenvatinib group and 1.5% (2 patients) in the placebo arm. The median exposure duration was 13.8 months for lenvatinib and 3.9 months for placebo and the median time to response for lenvatinib was 2.0 months. Median OS has not yet been reached.
The six most common lenvatinib treatment-related adverse events (TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%), fatigue (59.0%), decreased appetite (50.2%), weight loss (46.4%) and nausea (41.0%). TRAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) included hypertension (41.8%), proteinuria (10.0%), weight loss (9.6%), diarrhoea (8.0%), and decreased appetite (5.4%).
About Thyroid Cancer
Thyroid cancer refers to cancer that forms in the tissues of the thyroid gland, located at the base of the throat near the trachea. It is more common in women than in men and most are in their 40s or 50s at time of diagnosis.
Thyroid cancer affects more than 52,000 people in Europe each year. The incidence of thyroid cancer has increased significantly in the last decade by 69% and 65% in men and women, respectively. The most common types of thyroid cancer, papillary and follicular (including Hurthle cell), are classified as differentiated thyroid cancer (DTC) and account for approximately 85-90% of all cases.,, The remaining cases are classified as either medullary (3-4% of cases) or anaplastic (1-2% of cases).,
About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology.
As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.
For more information about Eisai Co., Ltd., please visit http://www.eisai.com.
- SPC Lenvima. Available at: http://www.ema.europa.eu. Accessed: December 2015
- EUCAN 2015. http://eu-cancer.iarc.fr/EUCAN/Cancer.aspx?Cancer=35. Accessed: December 2015
- Kilfoy BA et al. Cancer Causes Control. 2009 Jul;20(5):525-31
- Butterfly Thyroid Cancer Trust. About Thyroid Cancer. Available at : http://www.butterfly.org.uk/about.htm Accessed: December 2015
- Matsui J, et al. Clin Cancer Res 2008;14:5459-65
- Matsui J, et al. Int J Cancer 2008;122:664-71
- Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Med. Chem. Lett 2015;6:89-94
- Wu P. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discovery Today, July 2015; 1-6
- Guo et al. Overall Survival gain with lenvatinib vs. placebo in radioactive iodine refractory differentiated thyroid cancer (RR-DTC): an updated analysis. Presented at ECC 2015.
- Schlumberger M et al. Lenvatinib versus placebo in radioiodine refractory differentiated thyroid cancer. NEJM 2015; 372: 621-630. Available at http://www.nejm.org/doi/full/10.1056/NEJMoa1406470 Accessed: December 2015
- National Cancer Institute at the National Institute of Health. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 [http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages ]. Accessed: December 2015
- Brito J et al. BMJ 2013; 347
- Cancer Research UK. Thyroid cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/thyroid/incidence/uk-thyroid-cancer-incidence-statistics Accessed: December 2015
- Pacini F et al. ESMO Guidelines Working Group. Ann Oncol. 2012;23(suppl 7):vii110-vii119
- Thyroid Cancer Basics. 2011, Available at: http://www.thyca.org. Accessed: December 2015
- Cooper DS et al; Thyroid. 2009;19:1167-1214
- National Cancer Institute. Medullary Thyroid Cancer. Available at http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/HealthProfessional/page7. Accessed: December 2015