Eisai and Purdue Pharma Announce Positive Topline Results of SUNRISE 2, the Second Phase 3 Pivotal Study of Lemborexant

Long-term efficacy and safety evaluation in patients with insomnia, a sleep-wake disorder, met primary and key secondary efficacy objectives?

TOKYO and STAMFORD, Conn. – October 17, 2018 – Eisai Co., Ltd. (CEO: Haruo Naito, “Eisai”) and Purdue Pharma L.P. (President and CEO: Craig Landau, “Purdue Pharma”) today announced positive topline results from SUNRISE 2, a long-term Phase 3 efficacy and safety evaluation of lemborexant, an investigational agent for sleep-wake regulation currently being studied for the potential treatment of multiple sleep-wake disorders. Topline results reported today are the primary and key secondary outcomes of the study from the six-month, placebo-controlled treatment period; the study is ongoing to 12 months. Eisai and Purdue Pharma plan to present full results from SUNRISE 2 at upcoming medical meetings in 2019.

SUNRISE 2 enrolled more than 900 adult patients (18 to 88 years of age) with insomnia disorder, characterized by difficulty falling asleep and/or staying asleep. The study met the pre-specified primary and key secondary efficacy objectives assessed by patient self-reports (sleep diaries). At the end of the six-month, placebo-controlled treatment period, lemborexant 5 mg and 10 mg provided statistically significant improvement in subjective sleep onset latency compared to placebo, the study’s primary endpoint. Lemborexant 5 mg and 10 mg also provided statistically significant improvement in sleep maintenance variables of subjective sleep efficiency and subjective wake after sleep onset compared to placebo, which were the study’s key secondary endpoints. Daily functioning, as measured by the Insomnia Severity Index, was also improved by both lemborexant 5 mg and 10 mg compared to placebo. The most common adverse events (AEs), greater than 5 percent in either lemborexant treatment arm and greater than placebo, were somnolence, headache, and influenza. Overall discontinuation rates due to AEs were comparable between placebo and lemborexant 5 mg, and higher for lemborexant 10 mg.

“As a clinician and researcher treating patients with insomnia and other sleep-wake disorders for 30 years, for me, successful treatment means that patients fall asleep fast, sleep well, and wake well, without functional impairment, or loss of effect over time,” said Russell Rosenberg, PhD, D.ABSM, a Principal Investigator in the lemborexant studies and former Chairman of the Board of the National Sleep Foundation. “The results of SUNRISE 2 are particularly encouraging for the many patients who suffer from chronic insomnia.”

The results of SUNRISE 2 build on a growing body of knowledge supporting the development of lemborexant, including SUNRISE 1, a recently completed Phase 3 study of lemborexant 5 mg and 10 mg versus placebo, including a superiority comparison to zolpidem tartrate extended release (zolpidem ER) as a secondary endpoint, as well as key safety studies evaluating for impairment as assessed by the ability to maintain postural stability – a predictor of risk for falls – after middle-of-the-night and next morning awakening and next-morning driving performance.

“Our aspiration for lemborexant is to bring to the millions of patients suffering from insomnia and other sleep-wake disorders an agent for sleep-wake regulation that improves their ability to fall asleep and stay asleep, and maintains efficacy over time,” said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. “In SUNRISE 2, lemborexant improved time to sleep onset and sleep maintenance over a six-month period. With these results, we now look forward to proceeding with regulatory submissions for lemborexant to bring to patients a long-term treatment option for treating the sleep-wake disorder, insomnia.”

Lemborexant acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening wakefulness without impeding the ability to awaken to external stimuli.

“We understand the importance of sleep-wake regulation to overall health and patient outcomes and, alongside our collaboration partner, Eisai, look forward to continued research as part of our commitment to a variety of patient populations with sleep-wake disorders,” said Marcelo Bigal, MD, PhD, Chief Medical Officer, Purdue Pharma.

Discovered by Eisai, lemborexant is being jointly developed by Eisai and Purdue Pharma. Information about ongoing clinical studies is available at clinicaltrials.gov.

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agent will successfully complete clinical development or gain health authority approval.

Media Inquiries
Eisai Co., Ltd. ? ? ?????????? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ??Purdue Pharma L.P.
Public Relations Department????????????????????? ?? Danielle Lewis
TEL: +81-(0)3-3817-5120???????????????????????????? TEL: +1-203-588-7653

<Notes to editors>

1. About lemborexant
Lemborexant, an investigational dual orexin receptor antagonist, is Eisai’s in-house discovered and developed small molecule compound which inhibits orexin neurotransmission, or signaling, by binding competitively to two subtypes of orexin receptors (orexin receptor 1 and 2). In individuals with sleep-wake disorders, it is possible that the orexin system which regulates wakefulness is not functioning normally. During normal periods of sleep, orexin system activity is suppressed, suggesting it is possible to purposefully counteract inappropriate wakefulness and facilitate the initiation and maintenance of sleep.

Eisai and Purdue Pharma are investigating lemborexant as a potential treatment option for insomnia and other sleep-wake disorders. A Phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder and mild to moderate Alzheimer’s dementia is underway.

2.?About SUNRISE 2 / Study 303¹
A 12-month multicenter, global, randomized, controlled, double-blind, parallel group study of 971 male or female adult participants (18 to 88 years of age) with insomnia disorder,?including a screening and two-week placebo run-in period, a 52-week treatment period and a two-week follow-up period. All patients received lemborexant for at least six months during the study.?Lemborexant 5 mg, 10 mg or matching placebo was taken orally in tablet form at home each night immediately before the patient intended to try to sleep for the first six months of study. The primary outcome measure was mean change from baseline in subjective sleep onset latency after six months of placebo-controlled treatment. Key secondary outcome measures were mean change from baseline in subjective sleep efficiency and subjective wake after sleep onset after six months of placebo-controlled treatment.

3.?About Sleep Disorders
Population studies show that sleep disorders affect many more people worldwide than previously thought.¹?Insomnia disorder is characterized by difficulty falling sleep, staying asleep or both, despite an adequate opportunity to sleep, that can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.^3,4?Insomnia disorder is the most common sleep disorder, with persistent insomnia symptoms experienced by approximately 10 percent of the adult population.^2,3
Sleeping well is essential for good health, including brain health. Poor sleep is associated with a wide range of health consequences, including an increased risk of hypertension, accidental injury, diabetes, obesity, depression, heart attack, stroke and dementia, as well as adverse effects on mood and behavior.^4,5
Experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases and mortality.^2,6?Studies suggest an optimal sleep duration between seven and eight hours.^2,6?Women are 1.4 times more likely than men to suffer from insomnia.⁷
Older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent waking and early waking, that can lead to less sleep time.⁸
4. 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 approximately 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our?hhc?philosophy by delivering innovative products to address unmet medical needs, with a particular focus in our strategic areas of 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?www.eisai.com/.

5. About Purdue Pharma L.P.
Purdue Pharma L.P. develops and provides prescription medicines that meet the evolving needs of healthcare professionals, patients, and caregivers. We were founded by physicians and we are currently led by a physician. Beyond our efforts to provide quality medications, Purdue is committed to supporting?national, regional and local collaborations to drive innovations in patient care. Privately held, Purdue is pursuing a pipeline of new medications and technologies through internal research & development and strategic industry partnerships. For more information, please visit?www.purduepharma.com.

References¹?Eisai Inc. Long-term study of lemborexant in insomnia disorder (E2006-G000-303). Available from?https://clinicaltrials.gov/ct2/show/NCT02952820.?NLM identifier: NCT02952820.²?Ferrie JE, et al. Sleep epidemiology – a rapidly growing field.?Int J Epidemiol. 2011;40(6):1431–1437.³?Ohayon MM, et al. Epidemiology of insomnia: what we know and what we still need to learn.?Sleep Med Rev.?2002;6(2):97-111.
⁴?Institute of Medicine. Sleep disorders and sleep deprivation: An unmet public health problem. Washington, DC: National Academies Press. 2006.⁵?Pase MP, Himali JJ, Grima NA, et al. Sleep architecture and the risk of incident dementia in the community.?Neurology. 2017;89(12):1244-1250.⁶?Trenell MI, et al. Sleep and metabolic control: waking to a problem??Clin Exp Pharmacol Physiol.?2007;34:1-9.
⁷?Zhang B, Wing, YK. Sex differences in insomnia: a meta-analysis.?Sleep.?2006;29(1):85-93.
⁸?Ohayon MM, et al. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan.?Sleep. 2004;27:1255-1273.

NEW DRUG APPLICATION FOR PERAMPANEL FOR ADJUNCTIVE TREATMENT OF PARTIAL ONSET SEIZURES ACCEPTED IN CHINA

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) has announced that the National Medical Products Administration of China has accepted for review a New Drug Application for Eisai’s antiepileptic drug (AED) perampanel (generic name, product name: Fycompa^?) as an adjunctive treatment for partial onset seizures in epilepsy patients 12 years of age and older. This NDA is the first to be submitted for perampanel in China.

This application for perampanel in partial onset seizures in China was based on the results of three Phase III clinical studies conducted mainly in Europe and the United States, as well as the results of a Phase III clinical study (Study 335) conducted mainly in Asia including China and Japan.
In China it is estimated that there are approximately 9 million patients with epilepsy, with approximately 60% being affected by partial-onset seizures, and 40% of these patients with partial-onset seizures require adjunctive treatment.¹?As approximately 30% of patients with epilepsy are unable to control their seizures with currently available AEDs,²?this is a disease with significant unmet medical need.

Perampanel is a first-in-class AED discovered at Eisai’s Tsukuba Research Laboratories. Administered orally once-daily, it is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at AMPA receptors on postsynaptic membranes.

Perampanel has been approved in over 55 countries around the world as an adjunctive treatment for partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older. In addition, perampanel has been approved in over 50 countries around the world as an adjunctive treatment for primary generalized tonic clonic seizures in patients with epilepsy 12 years of age and older. In the United States, perampanel is also indicated for monotherapy and adjunctive use in the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 4 years of age and older.

Eisai considers neurology including epilepsy, a therapeutic area of focus, and is striving to deliver perampanel to patients in China as soon as possible. In pursuit of our mission to provide “seizure freedom” to a greater number of patients living with epilepsy, Eisai seeks to address the diverse needs of, as well as increasing the benefits provided to, patients with epilepsy and their families.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

[Notes to editors]
1. About perampanel (generic name, product name: Fycompa)
Perampanel is a first-in-class AED discovered and developed by Eisai. With epileptic seizures being mediated by the neurotransmitter glutamate, the agent is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at AMPA receptors on postsynaptic membranes. Perampanel is available in tablet form to be taken once daily orally at bedtime. In addition, an oral suspension formulation has been approved in the United States.

Perampanel is currently approved in more than 55 countries and territories, including the United States, Japan, in Europe and in Asia as adjunctive treatment for partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 12 years of age and older. An application seeking approval for use in the treatment of partial-onset seizures has now been filed in China. In addition, perampanel has been approved in more than 50 countries, including the United States, Japan, in Europe and in Asia for treatment as an adjunctive therapy for primary generalized tonic clonic seizures in patients with epilepsy 12 years of age and older. In the United States, perampanel is also indicated for monotherapy and adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older.

Furthermore, Eisai is conducting a global Phase III clinical study (Study 338) for the agent in patients with seizures associated with Lennox-Gastaut syndrome. In Japan and Europe, Eisai is conducting a Phase III study in pediatric patients with epilepsy (Study 311). Additionally, a Phase III study of perampanel as monotherapy in untreated patients with partial-onset seizures 12 years of age and older is being conducted in Japan (Study 342).

2. About Study 335 upon which the NDA in China was based³

Study title:	A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to?Evaluate the Efficacy and Safety of Perampanel Administered as an Adjunctive Therapy in Subjects with Refractory Partial-onset Seizures
Study population:	710 patients aged 12 years and older who have a diagnosis of epilepsy with partial-onset?seizures with or without secondarily generalized seizures receiving one to a maximum of three anti-epileptic drugs
Treatment administered:	Perampanel oral tablets, 4 mg/day, 8 mg/day and 12 mg/day, once daily before bedtime Perampanel-matched placebo oral tablets, once daily before bedtime
Duration of treatment:	Prerandomization Phase: 6 weeks Randomization Phase (treatment): 19 weeks (Titration Period, 6 weeks; Maintenance Period, 13 weeks) Extension Phase: over 10 weeks
Study locations:	Japan, China, South Korea, Australia, Thailand, Malaysia, Chinese Taiwan
Primary endpoint:	Percent change in seizure frequency per 28 days during treatment relative to baseline
Results:	The percent change in seizure frequency in the placebo group was -10.8% while in the?perampanel (4 mg, 8 mg, 12 mg) groups it was -17.3%, -29.0% and -38.0%, respectively. The difference between perampanel and placebo was statistically significant for the perampanel 8 and 12 mg groups (p=0.0003 for 8 mg, p<0.0001 for 12 mg).
Adverse events:	The most common adverse events (≥10% in the perampanel arms and greater than?placebo) were dizziness (22.7%, 28.6%, 42.2% in the perampanel 4 mg, 8 mg, 12 mg groups respectively and 5.7% for placebo) and somnolence (15.9%, 17.7%, 17.8% in the perampanel 4 mg, 8 mg, 12 mg groups respectively and 13.1% for placebo).

3. About Epilepsy
Epilepsy affects approximately 3.4 million people in the United States, 1 million people in Japan, 6 million people in Europe, 9 million people in China, and approximately 60 million people worldwide. As approximately 30% of patients with epilepsy are unable to control their seizures with currently available AEDs,²?this is a disease with significant unmet medical need.

Epilepsy is broadly categorized by seizure type, with partial-onset seizures accounting for approximately 60% of epilepsy cases and generalized seizures accounting for approximately 40%. In a partial-onset seizure, an abnormal electrical disturbance occurs in a limited area of the brain, and may subsequently spread throughout the brain, becoming a generalized seizure (known as a secondarily generalized seizure). In a generalized seizure, abnormal electrical disturbances occur throughout the brain, and can be followed by a loss of consciousness or physical symptoms manifested throughout the whole body.

¹? Clinical Guideline 2015 in China
²? “The Epilepsies and Seizures: Hope Through Research. What are the epilepsies?” National Institute of Neurological Disorders and Stroke, accessed May 24, 2016,?http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm#230253109
³? Nishida T., et al. Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study.?Acta Neurol Scand.?2018; 137:392-399

EISAI AND MERCK & CO., INC., KENILWORTH, N.J., U.S.A. ANNOUNCE CHINA NATIONAL MEDICAL PRODUCTS ADMINISTRATION (NMPA) APPROVAL OF LENVIMA? (LENVATINIB) FOR TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARC

First Approval for LENVIMA in China and First New Therapy for the First-line Treatment of Unresectable HCC Approved in China in a Decade

TOKYO and KENILWORTH, N.J. Sept. 5, 2018 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Merck & Co., Inc., Kenilworth N.J., U.S.A., known as MSD outside of the United States and Canada, announced today 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,¹?and the first new systemic therapy approved for the first-line treatment of unresectable HCC in China in ten years.¹

The approval was based on results from the REFLECT study (Study 304)², 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. 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, HKSA and Chinese Taiwan), LENVIMA demonstrated efficacy based on non-inferiority of OS compared to sorafenib, with improvements also observed in PFS, TTP and ORR³. Approximately 80% 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. (For the detailed data, please refer to “Notes for Editors” below.)

In the China package insert, the five most common adverse reactions observed in patients treated with LENVIMA were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%) and decreased weight (31%), 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% 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.¹?HCC accounts for 85% to 90% 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. Today, 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.

*¹?Overall Survival (OS): The time period from the commencement of cancer treatment up until death by any cause. Whether the cause of death is cancer or not is not taken into consideration for this variable.
*²?Progression Free Survival (PFS): PFS is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.
*³?Time To Progression: TTP is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression. Unlike PFS, TTP does not consider death from any cause.
*⁴?Objective Response Rate (ORR): ORR is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.

Contacts

?

Eisai Public Relations
+81-(0)3-3817-5120

Eisai Investor Relations
+81-(0)3-3817-3016

Merck Media Relations
Pamela Eisele:?(267) 305-3558
Ann Bush: (908) 740-6677

Merck Investor Relations
Teri Loxam: (908) 740-1986
Michael DeCarbo: (908) 740-1807

– Notes for Editors –

About the REFLECT Trial (Study 304)?²

REFLECT was a large (n=954) Phase 3, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of LENVIMA versus sorafenib as a first-line systemic treatment in patients with unresectable HCC. Patients at 154 trial sites in 20 countries were randomized to receive LENVIMA ?12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was OS, tested first for non-inferiority to sorafenib, then for superiority.?The key secondary efficacy endpoints of this study included PFS, TTP and ORR, tested for superiority to sorafenib.

In the China package insert, REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio [HR]: 0.92; 95% Confidence Interval [CI]: 0.79-1.06). Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. In addition, LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS, TTP and ORR, as confirmed by a blinded independent imaging review:

Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.00001) per blinded independent imaging review based on mRECIST criteria.
Median TTP was doubled with LENVIMA compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.00001) per blinded independent imaging review based on mRECIST criteria.
LENVIMA showed nearly 3.5 times the ORR of sorafenib: 40.6% (95% CI: 36.2-45.0) versus 12.4% (95% CI: 9.4-15.4) per blinded independent imaging review based on mRECIST criteria (odds ratio 5.01, 95% CI: 3.59-7.01; p<0.00001).

?
About the Subpopulation Analysis of Patients from the Greater Chinese?Region³

The results of subpopulation analysis of patients from the greater?Chinese region³were based on 288 patients out of the 954 HCC patients who participated in the REFLECT study. In this subpopulation analysis, median OS was 15.0 months for LENVIMA versus 10.2 months for sorafenib (HR: 0.73; 95% CI: 0.55-0.96; nominal p=0.02620). Independent imaging review based on mRECIST criteria revealed the following results: PFS (LENVIMA 8.4 months versus sorafenib 3.6 months in median [HR: 0.47; 95% CI: 0.35-0.64; nominal p<0.00001]), TTP (LENVIMA 9.2 months versus sorafenib 3.6 months in median [HR: 0.45; 95% CI: 0.33-0.62; nominal p<0.00001]) and ORR (LENVIMA 43.8% versus sorafenib 13.2% [odds ratio 5.14; 95% CI: 2.84-9.31; nominal p<0.00001]).

Additionally, of the 288 patients in the subpopulation, approximately 80% (n=242) were living with HCC resulting from HBV. An analysis of these patients revealed the following results for OS: LENVIMA (n=123) 14.9 months versus sorafenib (n=119) 9.9 months in median (HR: 0.72; 95% CI: 0.53-0.97).

About Unresectable Hepatocellular Carcinoma (HCC)?

Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for 750,000 deaths per year globally. Additionally, 780,000 cases are newly diagnosed each year.²?There is a large regional difference, with about 80% of new cases occurring in Asian regions, including China and Japan. HCC accounts for 85% to 90% of primary liver cancer cases. HCC is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include hepatitis B virus and hepatitis C virus. However, according to a recent investigation, non-B/non-C HCC is on the rise. Surgery is the first option for treatment, but for patients with unresectable HCC who are not amenable for potentially curative therapeutic interventions, which include liver transplant, surgical resection and tumor ablation (typically radiofrequency ablation or cryotherapy), or who are not suitable for transarterial chemoembolization (TACE), treatment options are limited and the prognosis is very poor.

About LENVIMA^??(lenvatinib mesylate)?

Discovered and developed in-house by Eisai, LENVIMA is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi 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 pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, Eisai has obtained approval for LENVIMA as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a second-line treatment for RCC in over 45 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx^??for RCC.

In addition, LENVIMA has been approved as a treatment for hepatocellular carcinoma in Japan, the United States, Europe and South Korea. Eisai has submitted applications for an indication covering hepatocellular carcinoma in Chinese Taiwan (December 2017), as well as in other countries.

It is important to note that the dose for LENVIMA for patients with unresectable HCC is based on the patient’s weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

About the Eisai and Merck?& Co., Inc., Kenilworth, N.J., U.S.A.?Strategic Collaboration

In March 2018, Eisai and Merck?& Co., Inc., Kenilworth, N.J., U.S.A, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA.?Under the agreement, the companies will jointly develop and commercialize LENVIMA, both as monotherapy and in combination with?Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s anti-PD-1 therapy KEYTRUDA^?(pembrolizumab). In addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the LENVIMA and KEYTRUDA combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types. The LENVIMA and KEYTRUDA combination is not approved in any cancer types today.

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?philosophy. With approximately 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our?human health care?philosophy by delivering innovative products in various 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?www.eisai.com.

Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s?Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck & Co., Inc., Kenilworth, N.J., U.S.A., the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment.

As part of our focus on cancer, Merck & Co., Inc., Kenilworth, N.J., U.S.A. is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit?www.merck.com/clinicaltrials.

About Merck?& Co., Inc., Kenilworth, N.J., U.S.A.

For more than a century, Merck & Co., Inc., Kenilworth, N.J., U.S.A., a leading global biopharmaceutical company known as MSD outside of?the United States?and?Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck & Co., Inc., Kenilworth, N.J., U.S.A. continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola.

For more information, visit?www.merck.com?and?connect with us on?Twitter,?Facebook,?Instagram,?YouTube?and?LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J.,?U.S.A.

This news release of Merck & Co., Inc., Kenilworth, N.J., U.S.A. (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2017 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

KEYTRUDA^??is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

¹?GLOBOCAN2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012.?http://globocan.iarc.fr/.
²?Kudo M et al., “Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial”?The Lancet?2018, 391 (10126), 1163-1173
³?The Package Insert of Lenvatinib Mesilate Capsules in China

LENVIMA? (LENVATINIB) CAPSULES APPROVED FOR FIRST-LINE TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC) IN SOUTH KOREA

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its South Korea subsidiary Eisai Korea Inc. received approval for the kinase inhibitor LENVIMA^??(lenvatinib mesylate) as a single agent for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) from the Ministry of Food and Drug Safety (MFDS) in South Korea. An application seeking approval of LENVIMA for use in the treatment of unresectable HCC was submitted in South Korea in March 2018. This approval for LENVIMA in South Korea marks the second in Asia following approval in Japan. LENVIMA is the first new treatment option approved in ten years as a first-line systemic treatment for HCC in South Korea.
In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. The companies are expected to commence co-commercialization efforts for LENVIMA in South Korea by the end of 2018.

This approval was based on results from REFLECT (Study 304), an open-label, Phase III trial where LENVIMA demonstrated a treatment effect on overall survival (OS)*¹?by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC. LENVIMA also demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS)*²?and objective response rate (ORR)*³.

REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio [HR]: 0.92; 95% Confidence Interval [CI]: 0.79-1.06). The OS analysis was conducted as prespecified in the statistical analysis plan when 351 events had occurred in the LENVIMA arm and 350 events had occurred in the sorafenib arm. Regarding secondary efficacy endpoints, according to independent imaging review based on mRECIST criteria, LENVIMA showed statistically significant superiority and clinically meaningful improvements as compared to sorafenib in median PFS: LENVIMA 7.3 months versus sorafenib 3.6 months (HR: 0.64; 95% CI: 0.55-0.75; p<0.0001) and ORR: LENVIMA 40.6% versus sorafenib 12.4% (p<0.0001). The five most common adverse reactions observed in patients treated with LENVIMA were hypertension, diarrhea, decreased appetite, weight loss and fatigue, 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% of which occur in Asian regions.¹?HCC accounts for 85% to 90% 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.

LENVIMA has been 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 RCC in over 45 countries including the United States and in Europe.

Since the initial launch, more than 10,000 patients have been treated with LENVIMA, which is approved in more than 50 countries worldwide. In Japan, approximately 3,000 HCC patients have been treated with LENVIMA since the approval of the HCC indication in March 2018.

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, in collaboration with Merck & Co., Inc., Kenilworth, N.J., U.S.A., as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to cancer patients, their families, and healthcare providers worldwide.

*¹?Overall Survival (OS): The time period from the commencement of cancer treatment up until death by any cause. Whether the cause of death is cancer or not is not taken into consideration for this variable.

*²?Progression Free Survival (PFS): PFS is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.

*³?Objective Response Rate (ORR): ORR is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

[Notes to editors]
1.?About LENVIMA^??(lenvatinib mesylate)
Discovered and developed in-house by Eisai, LENVIMA is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi 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 pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, Eisai has obtained approval for LENVIMA as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a second-line treatment for RCC in over 45 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx^??for RCC.

In addition, LENVIMA has been approved as a treatment for hepatocellular carcinoma in Japan, the United States and Europe. Eisai has submitted applications for an indication covering hepatocellular carcinoma in China (October 2017, designated for Priority Review and Approval in December 2017), Chinese Taiwan (December 2017), and other countries.

It is important to note that the dose for LENVIMA for patients with unresectable HCC is based on the patient’s weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

2. About the Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. Strategic Collaboration
In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA (lenvatinib). Under the agreement, the companies will jointly develop and commercialize LENVIMA, both as monotherapy and in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s anti-PD-1 therapy KEYTRUDA^??(pembrolizumab). In addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the LENVIMA and KEYTRUDA combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types.

3. About the REFLECT Trial (Study 304)?
REFLECT was a large (n=954) Phase III, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma (HCC). Patients at 154 trial sites in 20 countries were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival, tested first for non-inferiority to sorafenib, then for superiority. REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio [HR]: 0.92; 95% Confidence Interval [CI]: 0.79-1.06).

In addition, LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS and ORR, as confirmed by a blinded independent imaging review (IIR).

Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.0001) per blinded independent imaging review based on mRECIST criteria, and 7.3 months with LENVIMA versus 3.6 months with sorafenib (HR: 0.65; 95% CI: 0.56–0.77) per RECIST 1.1. LENVIMA showed nearly 3.5 times the ORR of sorafenib: 40.6% (95% CI: 36.2-45.0) (complete response [CR]=2% (n=10), partial response [PR]=38% (n=184)) vs. 12.4% (95% CI: 9.4-15.4) (CR=1% (n=4), PR=12% (n=55)) per blinded independent imaging review based on mRECIST criteria, respectively (p<0.0001), and 18.8% (95% CI: 15.3-22.3) with LENVIMA versus 6.5% (95% CI: 4.3-8.7) with sorafenib per RECIST 1.1.

In addition, median time to progression (TTP) was doubled with LENVIMA compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51-0.71; p<0.0001) per blinded independent imaging review based on mRECIST criteria, and 7.4 months with LENVIMA versus 3.7 months with sorafenib (HR: 0.61; 95% CI: 0.51-0.72; p<0.0001) per RECIST 1.1.

The results of the REFLECT trial were published in?The Lancet?2018, 391 (10126), 1163-1173 (published online on February 9, 2018).

4. About Unresectable Hepatocellular Carcinoma (HCC)
Liver cancer is the second leading cause of cancer related deaths and is estimated to be responsible for 750,000 deaths per year globally. Additionally, 780,000 cases are newly diagnosed each year. There is a large regional difference, with about 80% of new cases occurring in Asian regions, including China and Japan.¹?HCC accounts for 85% to 90% of primary liver cancer cases. HCC is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include hepatitis B virus and hepatitis C virus. However, according to a recent investigation, non-B/non-C HCC is on the rise. Surgery is the first option for treatment, but for patients with unresectable HCC who are not amenable for potentially curative therapeutic interventions, which include liver transplant, surgical resection, and tumor ablation (typically radiofrequency ablation or cryotherapy), or who are not suitable for transarterial chemoembolization (TACE), treatment options are limited and the prognosis is very poor.

¹?GLOBOCAN2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/

KEYTRUDA^??is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

LONG-TERM CARDIOVASCULAR OUTCOMES DATA FOR ANTI-OBESITY AGENT BELVIQ? PRESENTED AT THE EUROPEAN SOCIETY OF CARDIOLOGY AND PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) has announced that results from the Cardiovascular Outcomes Trial (CAMELLIA-TIMI 61) in patients treated with lorcaserin hydrochloride (generic name, product name in the U.S.: BELVIQ^?, “BELVIQ”) were highlighted in an oral presentation at the European Society of Cardiology (ESC) Congress 2018 held in Munich, Germany, and concurrently published in the?New England Journal of Medicine, one of the world’s most influential medical journals.¹?BELVIQ is the first ever weight loss medication approved for chronic weight management which has been proven to not increase the incidence of major cardiovascular (CV) events in a dedicated long-term cardiovascular outcome trial.

This study was conducted at over 400 sites in eight countries including the United States in collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group, and is the largest cardiovascular outcome trial conducted to date for a weight loss medication. As the primary safety objective, the study assessed the incidence of major adverse cardiovascular events (MACE: defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in 12,000 overweight and obese adults with existing cardiovascular disease or type 2 diabetes mellitus (T2DM) with cardiovascular risk factors who were administered BELVIQ 10 mg twice-daily (median 3.3 years). Overall, the median age of patients in the study was 64 and the median body mass index (BMI) was 35kg/m², with 57% of patients at baseline having T2DM, 90% with hypertension, 94% with hyperlipidemia and 20% with chronic kidney disease. Approximately 75% of patients had established atherosclerotic CV disease.

At the time of study completion, MACE occurred in 364 of 6,000 patients in the BELVIQ arm (2.0%/year) and 369 of 6,000 patients in the placebo arm (2.1%/year; hazard ratio, 0.99; 95% confidence interval (CI), 0.85-1.14; non-inferiority margin, 1.4). This demonstrated that BELVIQ did not increase the incidence of MACE, and therefore the primary safety objective of statistical non-inferiority was met. Since the primary safety objective was met, the primary efficacy outcome of incidence of CV death, myocardial infarction, stroke hospitalization for unstable angina, heart failure or any coronary revascularization (MACE+) was also assessed. From the results, MACE+ occurred in 707 of 6,000 patients (4.1%/year) in the BELVIQ arm and in 727 of 6,000 patients in the placebo arm (4.2%/year). Although statistical superiority was not observed (p=0.55), statistical non-inferiority was confirmed (hazard ratio, 0.97; 95% CI, 0.87-1.07; non-inferiority margin, 1.4).

In exploratory assessments of the efficacy of BELVIQ, at one year, significantly more patients treated with BELVIQ versus placebo lost greater than or equal to five percent of body weight (39% vs. 17%; nominal p-value<0.001) or greater than or equal to ten percent of body weight (15% vs. 5%; nominal p-value<0.001).
The average change in weight from baseline was -4.2 kg with BELVIQ and -1.4 kg with placebo, translating to a 2.8 kg greater net weight loss with BELVIQ (nominal p-value<0.001).

Furthermore, treatment with BELVIQ (for a period of one year), on top of standard of care for the respective comorbid conditions in CAMELLIA-TIMI 61, was associated with statistically significant improvements in systolic blood pressure (placebo-subtracted difference -0.9 mm Hg), diastolic blood pressure (-0.8 mm Hg), heart rate (-1.0 beat per minute), low-density lipoprotein cholesterol (-1.2 mg/dL), triglycerides (-11.7 mg/dL) and non-high-density lipoprotein cholesterol (-2.6 mg/dL).

BELVIQ also reduced hemoglobin A1C (HBA1c) in patients with T2DM at baseline (placebo-subtracted difference -0.3%) and reduced the rate of new onset diabetes in patients with pre-diabetes at baseline (3.1%/year with BELVIQ versus 3.8%/year with placebo).

No significant differences were seen in the overall incidence of serious adverse events between BELVIQ and placebo (31% vs. 32%), and the overall safety profile for BELVIQ in CAMELLIA-TIMI 61 was consistent with that of the approved label. Dizziness, fatigue, headache, nausea and diarrhea were the most commonly reported adverse events in CAMELLIA-TIMI 61. Adverse events possibly leading to study discontinuation were more frequent with BELVIQ versus placebo (7.2% vs. 3.7%), with the most commonly reported adverse events in this category for BELVIQ being dizziness, fatigue, headache, diarrhea and nausea.

Further results of analyses of the study will be presented on October 4 at the European Association for Study of Diabetes (EASD) Annual Meeting held in Berlin, Germany.

By continuing to provide additional clinical and scientific information regarding BELVIQ, Eisai continues to make further contributions to address unmet medical needs and increase the benefits for patients and their families.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

[Notes to editors]
1. About lorcaserin hydrochloride (U.S. brand name: BELVIQ, once daily formulation U.S. brand name: BELVIQ XR)
Discovered and developed by Arena Pharmaceuticals, Inc. (Headquarters: California, United States, President and CEO: Amit D. Munshi), lorcaserin is a novel chemical entity that is believed to decrease food consumption and promote satiety by selectively activating serotonin 2C receptors in the brain. Activation of these receptors may help a person eat less and feel full after eating smaller amounts of food. Lorcaserin was approved in June 2012 by the FDA as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m²?or greater (obese) or 27 kg/m²?or greater (overweight) in the presence of at least one weight-related comorbid condition, and was launched in the United States under the brand name BELVIQ in June 2013 after receiving a final scheduling designation from the U.S. Drug Enforcement Administration (DEA). In addition, lorcaserin has been made available in South Korea via a third-party distributor from 2015. Lorcaserin was approved in Mexico in July 2016 and in Brazil in December 2016, with the same indication as for the United States.
Furthermore, BELVIQ XR, a once-daily formulation of lorcaserin aiming to increase convenience of administration for patients, was approved in the United States in July 2016.
In January 2017, Eisai acquired all of Arena’s rights to develop and market BELVIQ.
The most common adverse reactions observed in multiple Phase III clinical studies on lorcaserin were headache, dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycemia, headache, back pain, cough and fatigue in patients with diabetes. For further information on lorcaserin in the United States, including Important Safety Information (ISI), please visit the BELVIQ product website (http://www.belviq.com).

2. About the Cardiovascular Outcomes Trial, CAMELLIA-TIMI61 Study
The CAMELLIA (Cardiovascular?And?Metabolic?Effects of?Lorcaserin?In Overweight?And Obese Patients) TIMI 61 study was the largest double-blind, placebo-controlled, parallel-group Phase IIIB/IV study among weight loss medications. The primary safety objective was to evaluate the incidence of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction or stroke. If the primary safety objective was met, the efficacy objective was to evaluate the impact of lorcaserin on the incidence of MACE+, defined as MACE or hospitalization due to unstable angina or heart failure, or any coronary revascularization. Secondary objectives included evaluation for the potential to delay or prevent conversion to T2DM in patients with pre-diabetes or no diabetes at baseline and improvement of glycemic control in patients with T2DM.

3. About the TIMI Study Group
The TIMI Study Group is an Academic Research Organization based at Brigham and Women’s Hospital that has been leading practice-changing cardiovascular clinical trials for 30 years.

4. About The?New England Journal of Medicine
The?New England Journal of Medicine?(NEJM) is the world’s leading medical journal and website, published continuously for over 200 years. NEJM has the highest Journal Impact Factor of all general medical journals (2017?Journal Citation Reports^?, Clarivate Analytics, 2018).

¹?Bohula, E. A., Cardiovascular Safety of Lorcaserin in Overweight and Obese Patients, The?New England Journal of Medicine, 2018.

EUROPEAN COMMISSION GRANTS MARKETING AUTHORIZATION FOR LENVIMA? (LENVATINIB) AS FIRST-LINE TREATMENT IN ADULTS WITH ADVANCED OR UNRESECTABLE HEPATOCELLULAR CARCINOMA

TOKYO August 23, 2018 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Merck & Co., Inc., Kenilworth N.J., U.S.A., known as MSD outside of the United States and Canada, announced today that the European Commission (EC) has granted a marketing authorization for the oral receptor tyrosine kinase (RTK) inhibitor LENVIMA^??(lenvatinib mesylate) as a single agent for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy. This is the first new first-line treatment option for advanced or unresectable HCC to be approved in Europe in approximately 10 years.

This approval was based on results from REFLECT (Study 304), where LENVIMA demonstrated a treatment effect on overall survival (OS)*¹?by statistical confirmation of non-inferiority, as well as statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS)*²?and objective response rate (ORR)*³?when compared with sorafenib in patients with previously untreated unresectable HCC.

REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio (HR): 0.92; 95% Confidence Interval (CI): 0.79-1.06). The OS analysis was conducted as prespecified in the statistical analysis plan when 351 events had occurred in the LENVIMA arm and 350 events had occurred in the sorafenib arm. Regarding secondary efficacy endpoints, according to independent imaging review based on mRECIST criteria, LENVIMA showed statistically significant superiority and clinically meaningful improvements as compared to sorafenib in median PFS: LENVIMA 7.3 months versus sorafenib 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.0001) and ORR: LENVIMA 41% versus sorafenib 12% (p<0.0001).

In the EU package insert, the most frequently reported adverse reactions (occurring in ≥30% of patients) are hypertension (44.0%), diarrhoea (38.1%), decreased appetite (34.9%), fatigue (30.6%), and weight decreased (30.4%).

Liver cancer is the second leading cause of cancer-related death and is estimated to be responsible for 750,000 deaths per year globally, with 780,000 cases newly diagnosed each year.¹?HCC accounts for 85% to 90% of liver cancer cases. Treatment options for unresectable HCC are limited and the prognosis is poor, making this an area of high unmet medical need.

Currently, LENVIMA is also available under the product name Kisplyx^??in combination with everolimus for use in the treatment of renal cell carcinoma (second-line treatment) in Europe. LENVIMA is available for use in the treatment of thyroid cancer in over 50 countries including in Europe, Japan and the United States. ?In Japan, approximately 3,000 HCC patients have been treated with LENVIMA since the approval of the HCC indication in March 2018.

*¹?Overall Survival (OS): The time period from the commencement of cancer treatment up until death by any cause. Whether the cause of death is cancer or not is not taken into consideration for this variable.

*²?Progression Free Survival (PFS): PFS is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.

*³?Objective Response Rate (ORR): ORR is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.

Media Inquiries:
Eisai Co., Ltd.
Public Relations Department
+81-(0)3-3817-5120

?

About LENVIMA^??(lenvatinib mesylate)

Discovered and developed in-house by Eisai, LENVIMA is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi 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 pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, Eisai has obtained approval for LENVIMA as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a second-line treatment for RCC in over 45 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx^??for RCC.

In addition to Europe, LENVIMA has been approved as a treatment for hepatocellular carcinoma in Japan (March 2018) and the United States (August 2018) as well. Eisai has submitted applications for an indication covering hepatocellular carcinoma in mainland China (October 2017), Chinese Taiwan (December 2017) and other countries.

It is important to note that the dose for LENVIMA for patients with unresectable HCC is based on the patient’s actual weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

About the Eisai and Merck?& Co., Inc., Kenilworth, N.J., U.S.A.?Strategic Collaboration

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA (lenvatinib). Under the agreement, the companies will jointly develop and commercialize LENVIMA, both as monotherapy and in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s anti-PD-1 therapy KEYTRUDA^??(pembrolizumab). In addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the LENVIMA/KEYTRUDA combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types.

About the REFLECT Trial (Study 304)

REFLECT was a large (N=954) Phase III, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma (HCC). Patients at 154 trial sites in 20 countries were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival, tested first for non-inferiority to sorafenib, then for superiority. Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. In addition, LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS and ORR, as confirmed by a blinded independent imaging review (IIR).

Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.0001) per blinded independent imaging review based on mRECIST criteria, and 7.3 months with LENVIMA versus 3.6 months with sorafenib (HR: 0.65; 95% CI: 0.56–0.77; p<0.0001) per RECIST 1.1. LENVIMA showed nearly 3.5 times the ORR of sorafenib: 41% (95% CI: 36-45) (complete response (CR)=2.1% (n=10), partial response (PR)=38.5% (n=184)) vs. 12% (95% CI: 9-15) (CR=0.8% (n=4), PR=11.6% (n=55)) per blinded independent imaging review based on mRECIST criteria, respectively (p<0.0001), and 19% (95% CI: 15-22) with LENVIMA versus 7% (95% CI: 4-9) with sorafenib per RECIST 1.1. In addition, median time to progression (TTP) was doubled with LENVIMA compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.0001) per blinded independent imaging review based on mRECIST criteria, and 7.4 months with LENVIMA versus 3.7 months with sorafenib (HR: 0.61; 95% CI: 0.51–0.72; p<0.0001) per RECIST 1.1.

The results of the REFLECT trial were published in?The Lancet?2018,?391?(10126), 1163-1173 (published online on February 9, 2018).

About Unresectable Hepatocellular Carcinoma (HCC)

Liver cancer is the second leading cause of cancer related deaths and is estimated to be responsible for 750,000 deaths per year globally. Additionally, 780,000 cases are newly diagnosed each year.¹?There is a large regional difference, with about 80% of new cases occurring in Asian regions, including China and Japan. Hepatocellular carcinoma accounts for 85% to 90% of primary liver cancer cases. Hepatocellular carcinoma is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include hepatitis B virus and hepatitis C virus. However, according to a recent investigation, non-B/non-C hepatocellular carcinoma is on the rise. Early stage hepatocellular carcinoma is treatable by a wide variety of means, including surgery, radiofrequency ablation, ethanol injection, and chemoembolization therapy, but treatment options for unresectable hepatocellular carcinoma are limited and the prognosis is very poor, meaning that this is an area of high unmet medical need.

?^1??GLOBOCAN2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012.?http://globocan.iarc.fr/

Eisai China Inc. Awarded Great Suzhou Best Employer for Second Consecutive Years

On August 22, the “2018 Great Suzhou Best Employer Award Ceremony” was held at Suzhou Jinji Lake International Convention Center. Eisai China Inc. (ECI) has been accredited Great Suzhou Best Employer for second consecutive years. The “best employer” selection project has been organized for 5 years since 2013. It is now the most influential and appealing event in Suzhou for employer brand selection. This project has successfully attracted the participation of over one thousand enterprises and the attention of millions of employees and has become an annual ceremony for the display of employer brands in Suzhou.?

“Great Suzhou Best Employer” was Awarded to ECI for Second Consecutive Years

Eisai China Inc. is a pharmaceutical company wholly-owned by Eisai Co., Ltd. of Japan. Eisai China Inc. has been rooted in Suzhou Industrial Park for 22 years since 1996, importing and producing more than ten varieties of original drugs, mainly concentrating on neurology, oncology and gastrointestinal area. Eisai has always been committed to the corporate philosophy of?human health care?(hhc), providing Chinese doctors with supports on medical diagnosis and treatment and offering patients and their families high quality, environmental-friendly, safe and satisfactory products and services. To meet the growing demand for high quality drugs and high-speed business development in China, Eisai invested US$230 million in the construction and production of a new factory in Baiyu Road, Suzhou Industrial Park in 1996. The new factory covers a land area of 23,000 square meters. After two expansions, Eisai invested another US$120 million in 2010 to purchase a land in Xingpu Road, Suzhou Industrial Park for the construction of a new factory integrating R&D, production and logistics. The new factory covers an area of 130,000 square meters. In November 2014, the construction of a new parenteral facility was completed; in November 2017, the construction of an oral solid dose production facility was completed. In December 2017, Eisai obtained the Drug Manufacturing Certificate. In the future, the new factory will provide high quality and satisfactory products overseas as well as meeting the demand of Chinese patients for clinical medication.

“hhc” is the corporate philosophy that Eisai has always been adhering to. Every staff of Eisai spares 1% of the business time to “hhc”?activities. We get into communities and approach to patients, listening to the voice of patients and their families to know their sufferings so as to better satisfy the demands of patients. Eisai actively gives back to the society and takes on social responsibility. Eisai’s?hhc?activities, including “Eisai” with Love – Approaching the Elderly, Worry-free for Health with “Eisai” – Care for Patients with Gastropathy, Blood Donation for Children with Leukemia, and etc., have been recognized and praised by the society. Eisai has been given, for several times, the “Best Charity Project Award” and the “Most Responsible Enterprise for the society” of the Industrial Park. Meanwhile, Eisai has set up?Eisai China Scholarship with seven famous universities, with an accumulation of approximately RMB7.29 million yuan to students to inspire them to get into the medical and pharmaceutical industry.?

We have always been taking the improvement of employee capability as one of its long-term strategies. In order to enhance the sense of belonging of employees and strengthen corporate cohesion, we have set up the “Honorary Staff Award” for the employees who have been serving the company for 5, 10, 15 and 20 years respectively. By the end of March 2018, we have 23 employees work for the company for more than 20 years, 71 for above 15 years, 182 for above 10 years and 542 for above 5 years. Employees’ ability enhancement and loyalty are the greatest return and recognition for the company.?At Eisai,?employees have sound career development space and grow in sync with the company. We fully respect every employee, encourage knowledge innovation and strict ethical guidelines, and promote a cooperative working atmosphere. Under the harmonious labor relations, we have been given many awards, such as the “AAAA Labor Security Unit” in 2017. With its competitive compensation mechanism and sound welfare system, Eisai provides comprehensive care for its employees.?

EISAI AND MERCK & CO., INC., KENILWORTH, N.J., U.S.A. ANNOUNCE FDA APPROVAL OF LENVIMA? (LENVATINIB) CAPSULES FOR FIRST-LINE TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC)

TOKYO August 17, 2018 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Merck & Co., Inc., Kenilworth N.J., U.S.A., known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) approved the kinase inhibitor LENVIMA^??(lenvatinib mesylate) for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). This approval was based on results from REFLECT (Study 304), where LENVIMA demonstrated a proven treatment effect on overall survival (OS) *¹?by statistical confirmation of non-inferiority, as well as statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS) *²?and objective response rate (ORR) *³?when compared with sorafenib in patients with previously untreated unresectable HCC. This is the second approval of LENVIMA for use in the treatment of HCC following approval in Japan earlier this year, and the first new systemic therapy to be approved in the U.S. for the first-line treatment of unresectable HCC in approximately 10 years.

REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio (HR): 0.92; 95% Confidence Interval (CI): 0.79-1.06). The OS analysis was conducted as prespecified in the statistical analysis plan when 351 events had occurred in the LENVIMA arm and 350 events had occurred in the sorafenib arm. Regarding secondary efficacy endpoints, according to independent imaging review based on mRECIST criteria, LENVIMA showed statistically significant superiority and clinically meaningful improvements as compared to sorafenib in median PFS: LENVIMA 7.3 months versus sorafenib 3.6 months (HR: 0.64; 95% CI: 0.55-0.75; p<0.001) and ORR: LENVIMA 41% versus sorafenib 12% (p<0.001).

In the U.S. Package Insert, the most common adverse reactions (≥20%) observed in patients treated with LENVIMA were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism and nausea. The most common serious adverse reactions (≥2%) reported in patients treated with LENVIMA were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%) and decreased appetite (2%).

The most common adverse reactions (≥20%) observed in patients who received sorafenib were palmar-plantar erythrodysesthesia syndrome, diarrhea, fatigue, hypertension, abdominal pain, decreased appetite, rash, decreased weight and arthralgia/myalgia. The most common serious adverse reactions (≥2%) reported in patients who received sorafenib were ascites (2%) and abdominal pain (2%).

“Unresectable hepatocellular carcinoma is an extremely difficult-to-treat cancer, with no new first-line systemic therapy options for more than a decade,” said Dr. Ghassan Abou-Alfa, medical oncologist, Memorial Sloan Kettering Cancer Center. “REFLECT is the first-ever positive Phase III trial against an active comparator in unresectable HCC. The efficacy and safety data from REFLECT are important findings for oncologists and others in the multidisciplinary teams who treat liver cancer, as well as for our patients who are affected by it.”

Liver cancer is the second leading cause of cancer-related death and is estimated to be responsible for 750,000 deaths per year globally, with 780,000 cases newly diagnosed each year.¹?HCC accounts for 85% to 90% of liver cancer cases. Treatment options for unresectable HCC are limited, and the prognosis is very poor, making this an area of high unmet medical need.

LENVIMA, a kinase inhibitor, was first approved in the U.S. in February 2015 for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). In May 2016, LENVIMA was approved in the U.S. in combination with everolimus, for patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy. Under the collaboration, Eisai and Merck & Co., Inc., Kenilworth N.J., U.S.A. initiated co-commercialization activities for LENVIMA in the U.S. in June 2018. Since the initial launch, more than 10,000 patients were treated with LENVIMA, which is approved in more than 50 countries worldwide. In Japan, approximately 3,000 HCC patients have been treated with LENVIMA since the approval of the HCC indication in March 2018.

*¹?Overall Survival (OS): The time period from the commencement of cancer treatment up until death by any cause. Whether the cause of death is cancer or not is not taken into consideration for this variable.

*²?Progression Free Survival (PFS): PFS is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.

*³?Objective Response Rate (ORR): ORR is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.

Media Inquiries:
Eisai Co., Ltd.
Public Relations Department
+81-(0)3-3817-5120

About LENVIMA^??(lenvatinib mesylate)

Discovered and developed in-house by Eisai, LENVIMA is an orally administered kinase inhibitor with a novel binding mode that selectively inhibits the multi 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 pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, Eisai has obtained approval for LENVIMA as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a second-line treatment for RCC in over 45 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx^??for RCC.

In addition to the United States, LENVIMA has been approved as a treatment for hepatocellular carcinoma in Japan as well. Eisai has submitted applications for an indication covering hepatocellular carcinoma in Europe (July 2017), mainland China (October 2017), Chinese Taiwan (December 2017) and other countries.

It is important to note that the dose for LENVIMA for patients with unresectable HCC is based on the patient’s actual weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

About the Eisai and Merck?& Co., Inc., Kenilworth, N.J., U.S.A.?Strategic Collaboration

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA (lenvatinib). Under the agreement, the companies will jointly develop and commercialize LENVIMA, both as monotherapy and in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s anti-PD-1 therapy KEYTRUDA^??(pembrolizumab). In addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the LENVIMA/KEYTRUDA combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types.

About the REFLECT Trial (Study 304)

REFLECT was a large (N=954) Phase III, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma (HCC). Patients at 154 trial sites in 20 countries were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival, tested first for non-inferiority to sorafenib, then for superiority. Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. In addition, LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS and ORR, as confirmed by a blinded independent imaging review (IIR).

Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.001) per blinded independent imaging review based on mRECIST criteria, and 7.3 months with LENVIMA versus 3.6 months with sorafenib (HR: 0.65; 95% CI: 0.56–0.77) per RECIST 1.1. LENVIMA showed nearly 3.5 times the ORR of sorafenib: 41% (95% CI: 36-45%) (complete response (CR)=2.1% (n=10), partial response (PR)=38.5% (n=184)) vs. 12% (95% CI: 10-16%) (CR=0.8% (n=4), PR=11.6% (n=55)) per blinded independent imaging review based on mRECIST criteria, respectively (p<0.001), and 19% (95% CI: 15-22) with LENVIMA versus 7% (95% CI: 4-9) with sorafenib per RECIST 1.1. In addition, median time to progression (TTP) was doubled with LENVIMA compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.0001) per blinded independent imaging review based on mRECIST criteria, and 7.4 months with LENVIMA versus 3.7 months with sorafenib (HR: 0.61; 95% CI: 0.51–0.72; p<0.0001) per RECIST 1.1. The results of the REFLECT trial were published in?The Lancet?2018,?391?(10126), 1163-1173 (published online on February 9, 2018).

About Unresectable Hepatocellular Carcinoma (HCC)

Liver cancer is the second leading cause of cancer related deaths and is estimated to be responsible for 750,000 deaths per year globally. Additionally, 780,000 cases are newly diagnosed each year.¹?There is a large regional difference, with about 80% of new cases occurring in Asian regions, including China and Japan. Hepatocellular carcinoma accounts for 85% to 90% of primary liver cancer cases. Hepatocellular carcinoma is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include hepatitis B virus and hepatitis C virus. However, according to a recent investigation, non-B/non-C hepatocellular carcinoma is on the rise. Early stage hepatocellular carcinoma is treatable by a wide variety of means, including surgery, radiofrequency ablation, ethanol injection, and chemoembolization therapy, but treatment options for unresectable hepatocellular carcinoma are limited and the prognosis is very poor, meaning that this is an area of high unmet medical need.

?^1?GLOBOCAN2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012.?http://globocan.iarc.fr/

Eisai (China) Listed for the Third Consecutive Year in China Top 100 Pharmaceutical Companies

Aug. 4, 2018, China Top 100 Pharmaceutical Enterprises List was released in the 35^thChina Pharmaceutical Industry Information Annual Conference 2018. Following the 97^th?place in 2015, and the 92^nd?place in 2016, Eisai (China) ranked 84^th?in the Top 100 List 2017.

Eisai China Holdings Ltd. ranked 84th in China Top 100 Pharmaceutical Enterprises List

With more than 20 years’ development, Eisai has established a development mode consisting of Eisai China Holdings Ltd. for capital control and management, while Eisai China Inc., Eisai (Liaoning) Pharmaceutical Co., Ltd. and Eisai (Suzhou) Trading Co., Ltd. for business support.?Currently, the total registered capital of Eisai in China is USD108.54 million. Eisai China specializes in neurology, oncology and gastrointestinal areas, and expands to the generic business. The sales volume reached RMB3 billion yuan in 2017.

“Eisai China always keeps to the faith in providing drugs with high quality and reasonable price and addressing the diverse needs of patients and their families. As an important strategy of EWAY 2025, Eisai China will actively expand the market coverage including the low-tier market,” said Ms. Yanhui Feng, Corporate Officer of Eisai Co. Ltd. and President of Eisai China Holdings Ltd. “Eisai China sticks, all the time, to the corporate philosophy that the interests of patients and their families are our priority and we will contribute to improving their well-beings, constantly bringing in high quality drugs, proactively expanding and innovating business mode, serving Chinese patients and their families.”

China Pharmaceutical Industry Information Annual Conference is held by China National Pharmaceutical Industry Information Center. Based on the Annual Statistic Report of China Pharmaceutical Industry published by Ministry of Industry and Information Technology, China Top 100 Pharmaceutical Enterprises List reflects the status of China pharmaceutical industry, with the final data obtained through the first, second, third and fourth reviews in the materials of pharmaceutical enterprises. According to the data analysis, with the constant expansion of the industrial scale of China’s pharmaceutical industry, the threshold of the top 100 enterprises in China’s pharmaceutical industry has increased year by year, and the lowest threshold of the top 100 enterprises has increased from RMB2.4 billion yuan of main business income in 2016 to RMB2.56 billion yuan in 2017. The overall size of the top 100 companies has continued to grow rapidly.

EISAI SIGNS COLLABORATION AGREEMENT FOR ANTI-OBESITY AGENT LORCASERIN IN CHINA TO CY BIOTECH

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has entered into an agreement to grant exclusive development and marketing rights for its anti-obesity agent lorcaserin hydrochloride (generic name, product name in the United States: BELVIQ^?, product name for once-daily formulation in the United States: BELVIQ XR^?, “l(fā)orcaserin”) in China (including HKSA and Chinese Macao) to CY Biotech (Headquarters: Taipei, Chinese Taiwan, “CYB”).

Under this agreement, Eisai will supply CYB with lorcaserin. Eisai will receive a one-time contractual payment and milestone payments dependent upon acquisition of regulatory approval. In addition, Eisai has the option rights to co-promote lorcaserin with CYB in China (excluding HKSA and Chinese Macao), as well as the option rights to market lorcaserin in HKSA and Chinese Macao.

Lorcaserin is a novel chemical entity that is believed to decrease food consumption and promote satiety by selectively activating serotonin 2C receptors in the brain. Lorcaserin was approved in June 2012 by the U.S. Food and Drug Administration (FDA) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m²?or greater (obese) or 27 kg/m²?or greater (overweight) in the presence of at least one weight-related co-morbid condition, and was launched in the United States in June 2013. Lorcaserin was approved in Mexico in July 2016 and in Brazil in December 2016, with the same indication as for the United States. In Chinese Taiwan, lorcaserin was developed by CYB, who obtained approval in July 2017 and launched lorcaserin in Chinese Taiwan in October 2017.

By entering into this agreement with CYB, which already has a track record in developing and marketing lorcaserin in Chinese Taiwan, Eisai is aiming to accelerate the delivery of lorcaserin to patients in these regions.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

[Notes to editors]

1. About lorcaserin hydrochloride (product name in the United States: BELVIQ, product name for once-daily formulation in the United States: BELVIQ XR, “l(fā)orcaserin”)
Discovered and developed by Arena Pharmaceuticals, Inc., lorcaserin is a novel chemical entity that is believed to decrease food consumption and promote satiety by selectively activating serotonin 2C receptors in the brain. Activation of these receptors may help a person eat less and feel full after eating smaller amounts of food. Lorcaserin was approved in June 2012 by the U.S. Food and Drug Administration (FDA) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m²?or greater (obese) or 27 kg/m²?or greater (overweight) in the presence of at least one weight-related co-morbid condition, and was launched in the United States under the brand name BELVIQ in June 2013 after receiving a final scheduling designation from the U.S. Drug Enforcement Administration (DEA). In addition, lorcaserin has been made available in South Korea via a third-party distributor from 2015. Lorcaserin was approved in Mexico in July 2016 and in Brazil in December 2016, with the same indication as for the United States. Furthermore, BELVIQ XR, a once-daily formulation of lorcaserin aiming to increase convenience of administration for patients, was approved in the United States in July 2016. In January 2017, Eisai acquired all of Arena’s rights to develop and market lorcaserin.

The most common adverse reactions observed in multiple Phase III clinical studies on lorcaserin were headache, dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycemia, headache, back pain, cough and fatigue in patients with diabetes.

A cardiovascular outcomes trial conducted in multiple countries, including the United States, with 12,000 patients found that long-term treatment with lorcaserin does not increase incidence of MACE (Major Adverse Cardiovascular Events including myocardial infarction, stroke and cardiovascular death), and the primary safety objective of the trial was met. In addition, regarding the incidence of MACE+ (consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina, heart failure or coronary revascularization) which was the primary efficacy endpoint, although statistical superiority to placebo was not met, the results successfully confirmed statistical non-inferiority for lorcaserin. In this trial, lorcaserin also demonstrated an improvement in multiple cardiovascular risk factors including blood pressure, lipids, blood glucose and renal function as well as a reduction in conversion to type 2 diabetes mellitus (T2DM) in patients without diabetes. Furthermore, in additional subgroup analyses, on a background of lifestyle modification, it was observed that lorcaserin improved long-term weight loss compared to placebo, including in subpopulations with T2DM and obstructive sleep apnea.

2. About?CY Biotech Company Ltd.

CY Biotech Company Ltd. (CYB) is a pharmaceutical company established in April 2011 with its headquarters in Chinese Taiwan. In 2012, CYB launched a wholly-owned subsidiary Chuang Yi Trading Limited in Shanghai. CYB obtained the exclusive rights for marketing and distributing lorcaserin in Chinese Taiwan and has been marketing lorcaserin in Chinese Taiwan since 2017. Aiming to be an innovative leader in self-paid pharmaceutical and health products with a wide range of indications, CYB is striving to improve the Quality of Life (QOL) of patients in Greater China.

Eisai and Purdue Pharma Announce Positive Topline Results of SUNRISE 2, the Second Phase 3 Pivotal Study of Lemborexant

NEW DRUG APPLICATION FOR PERAMPANEL FOR ADJUNCTIVE TREATMENT OF PARTIAL ONSET SEIZURES ACCEPTED IN CHINA

EISAI AND MERCK & CO., INC., KENILWORTH, N.J., U.S.A. ANNOUNCE CHINA NATIONAL MEDICAL PRODUCTS ADMINISTRATION (NMPA) APPROVAL OF LENVIMA? (LENVATINIB) FOR TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARC

LENVIMA? (LENVATINIB) CAPSULES APPROVED FOR FIRST-LINE TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC) IN SOUTH KOREA

LONG-TERM CARDIOVASCULAR OUTCOMES DATA FOR ANTI-OBESITY AGENT BELVIQ? PRESENTED AT THE EUROPEAN SOCIETY OF CARDIOLOGY AND PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE

EUROPEAN COMMISSION GRANTS MARKETING AUTHORIZATION FOR LENVIMA? (LENVATINIB) AS FIRST-LINE TREATMENT IN ADULTS WITH ADVANCED OR UNRESECTABLE HEPATOCELLULAR CARCINOMA

Eisai China Inc. Awarded Great Suzhou Best Employer for Second Consecutive Years

EISAI AND MERCK & CO., INC., KENILWORTH, N.J., U.S.A. ANNOUNCE FDA APPROVAL OF LENVIMA? (LENVATINIB) CAPSULES FOR FIRST-LINE TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC)

Eisai (China) Listed for the Third Consecutive Year in China Top 100 Pharmaceutical Companies

EISAI SIGNS COLLABORATION AGREEMENT FOR ANTI-OBESITY AGENT LORCASERIN IN CHINA TO CY BIOTECH

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