HATFIELD, England, March 9, 2016 /PRNewswire/ --
FOR ISRAELI AND UK MEDIA ONLY
From today, people in Israel with radioactive iodine refractory differentiated thyroid cancer (RAI refractory DTC) will have access to Lenvima® (lenvatinib), after the treatment received regulatory marketing authorisation and reimbursement from the country's health authorities. Advanced thyroid cancer is a difficult to treat condition with a poor prognosis and lenvatinib represents an important step forward for patients in Israel.
Lenvatinib is indicated 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)., Eisai will partner with the Neopharm group to ensure lenvatinib's availability to eligible patients in Israel.
Thyroid cancer incidence rates have increased in Israel over the past few decades. Although this type of cancer is relatively rare, numbers are rising and experts estimate that there are nearly 750 people in Israel living with thyroid cancer.
"The availability of lenvatinib in Israel means that people who live with advanced thyroid cancer, a typically hard-to-treat condition with limited effective treatment options, now have a new therapeutic option. Lenvatinib has a proven progression-free survival benefit versus placebo, which means patients may now have more time with their loved ones before their cancer progresses, something we know is very important for people with an advanced cancer," comments Dr Aron Popovtzer, Head of the Head and Neck Tumor Unit, Davidoff Center, Rabin's Beilinson Hospital, Israel.
"We welcome the chance to continue to work in partnership with Eisai to bring an important new treatment option to people living with advanced thyroid cancer across Israel," states Mr. Efi Shnaidman, General Manager, Neopharm Israel.
In the SELECT study, Lenvatinib demonstrated a statistically significant prolonged progression-free survival (PFS) in RAI refractory DTC versus placebo. Lenvatinib demonstrated a median 18.3 months progression free survival PFS versus 3.6 months for placebo (hazard ratio [HR] 0.21; 99% confidence interval 0.14-0.31, p<0.0001). In addition, the study underlines the rapid response of lenvatinib, with a median time to first objective response of two months. The New England Journal of Medicine published SELECT study, a randomised, double-blind, multicentre trial for people with progressive radioactive iodine refractory differentiated thyroid cancer (n=392). Lenvatinib significantly improves objective response rate versus placebo (64.8% versus 1.5%; p<0.0001). For lenvatinib, the most common treatment related adverse events were hypertension, diarrhoea, fatigue, decreased appetite, decreased weight, and nausea.
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.
Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, Switzerland, Europe, Israel, South Korea, Australia and Japan, and has been submitted for regulatory approval in Canada, Singapore, Russia, 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.
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. Data presented at ASCO 2014 and subsequently published in the New England Journal of Medicine showed that 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. The difference in OS between the groups was not significant. The confidence interval upper limit of 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%).
Subgroup analyses presented at the European Cancer Congress (ECC) 2015 show that lenvatinib with rank preserving structural failure time (RPSFT) model adjustment for crossover showed significantly improved overall survival versus placebo in patients with progressive radioactive iodine refractory differentiated thyroid cancer (RAI Refractory-DTC) (HR=0.53; 95% CI: 0.34, 0.82, nominal p=0.0051). The data showed that regardless of the time it took RAI Refractory-DTC patients to achieve an objective response (either at the time of the first tumour assessment (initial responders) or thereafter (subsequent responders)), their progression free survival (PFS) remained the same (HR=1.73; 95% CI: 0.95-3.15, p=0.07).
Subgroup analyses presented at the 15th International Thyroid Congress (ITC) 2015 showed that lenvatib improved progression free survival (PFS) for people with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC) regardless of metastatic site, with the exception of the brain. The sub-analysis observed response rates of more than 50% and a progression-free survival benefit among people treated with lenvatinib with common sites of metastasis (bone, liver, lung, lymph node).
A second analysis of the Phase III SELECT study at ITC 2015 demonstrated that lenvatinib maintains progression free survival irrespective of body mass index, as seen in a sub-analysis of three patient groups: under-and-normal weight (<25kg/m2), overweight (25-29.99 kg/m2), and obese (≥30 kg/m2). Obese patients who received lenvatinib exhibited the greatest progression free survival versus placebo (median PFS 16.7 months; HR 0.13; 95% CI 0.07-0.24; p<0.0001), but significant improvement in progression free survival was observed across all subgroups. Similarly lenvatinib showed comparable toxicities across all groups.
Two additional subanalyses from the SELECT study have been presented at the Endocrine Society Congress 2015 (ENDO). The first reports the results of the open-label extension phase of SELECT and aims to assess the crossover of patients in the placebo arm to the optional open-label lenvatinib treatment period. The results highlight that patients who crossed over from the placebo arm achieved a median PFS of 12.4 months with open-label lenvatinib 24mg starting dose treatment. Although toxicities were substantial to lenvatinib 24mg starting dose, these were generally managed with medications, dose interruption, and dose reductions.
The second abstract examines the relationship between thyroid abnormalities and their effect on the safety and efficacy outcomes in SELECT. The analysis shows that although an increase in thyroid-stimulating hormone (TSH) levels was a frequent complication, its direct relationship to lenvatinib therapy has not been established and there is no evidence TSH levels affect tumour responses to lenvatinib treatment.
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. Most people with thyroid cancer 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.
About Neopharm Group
Neopharm Group, established in 1941, through its family of companies, is engaged in the research and development, manufacturing and sales of a broad range of products in the health care field in 60 countries around the world. We embrace the promotion of innovative ideas, products and services to advance health and well-being. Our family of companies operates in three major segments: Pharmaceutical, Consumer Healthcare, and Medical.
The Pharmaceutical segment provides a complete spectrum of integrated services for international companies seeking to enter or expand their presence in the Israeli pharma, biotech and healthcare markets. For over 70 years we have grown the value of our products, consistently increased our turnover and enhanced our market leadership in Israel. We are considered the Israeli partner-of-choice and a one-stop-shop for multinational bio-pharma companies. Our success is based upon a track record of close collaboration with the world's leading multinational bio-pharma companies.
Neopharm is the exclusive representative and partner of leading multinational bio-pharma and consumer healthcare brands including: Abbott, Actelion, Alexion, Celgene, Johnson & Johnson, Pfizer Consumer Health among others.
Neopharm enjoys a sales turnover in excess of 400M $US in 2015 and employs 700 employees worldwide.
For further information please visit our web site: http://www.neopharmgroup.com
1. SPC Lenvima. Available at: http://www.medicines.org.uk/emc/medicine/30412 Accessed: November 2015
2. Eisai. Data on file. Lenvima SPC (Israel)
3. Lubina A, et al. Time trends of incidence rates of thyroid cancer in Israel: what might explain the sharp increase. Thyroid. 2006 Oct;16(10):1033-40.
4. International Agency for Research on Cancer (WHO) 2012. Globocan Worldwide Cancer statistics (WHO) 2012 1: 1 Available at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx Accessed February 2016
5. 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: November 2015
6. Matsui J, et al. Clin Cancer Res 2008;14:5459-65
7. Matsui J, et al. Int J Cancer 2008;122:664-671
8. Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Med. Chem. Lett 2015;6:89-94
9. Wu P. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discovery Today, July 2015; 1-6
10. Newbold K et al. The Influence of Time to Objective Response on Lenvatinib Clinical Outcomes in the Phase 3 SELECT Trial. Presented at ECC 2015
11. Habra, MA et al. Outcomes by Site of Metastasis for Patients With Radioiodine-refractory Differentiated Thyroid Cancer Treated With Lenvatinib Versus Placebo: Results from a Phase 3, Randomized Trial. 15th International Thyroid Congress 2015; Presented at the 15th International Thyroid Congress, October 2015
12. Tahara, M et al. Efficacy and Safety of Lenvatinib by Body Mass Index in Patients With 131I-Refractory Differentiated Thyroid Cancer From the Phase 3 SELECT Study. 15th International Thyroid Congress 2015; Presented at the 15th International Thyroid Congress, October 2015
13. Wirth L et al. 2015; Open-Label Extension Phase Outcomes of the Phase 3 Select Trial of Lenvatinib in Patients with 131I-Refractory Differentiated Thyroid Cancer. Endocrine Reviews; 36;2: Abstract 0R44-6. Available at: http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2015.THPTA.6.OR44-6 Accessed: November 2015
14. Schlumberger M et al. Relationship Between Thyroid-Stimulating Hormone Levels and Outcomes from the Randomized, Double-Blind, Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT). Available at: https://endo.confex.com/endo/2015endo/webprogram/Paper20459.html Accessed: November 2015
15. National Cancer Institute at the National Institute of Health. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 Accessed: November 2015
16. Brito J et al. BMJ 2013; 347
17. 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: November 2015
18. Gild M et al. Multikinase inhibitors: a new option for the treatment of thyroid cancer. Nature Reviews Endocrinology. 2011; 7: 617-624
19. National Cancer Institute. Medullary Thyroid Cancer. http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/HealthProfessional/page7 Accessed: November 2015
20. Thyroid Cancer Basics. 2011. Available at: http://www.thyca.org Accessed: November 2015
Date of preparation: March 2016
Job code: Lenvima-UK0066