Eisai Reports Continued Growth in China Driven by Lenvima and Fycompa Following Inclusion in National Reimbursement Drug List

Recently, Eisai announced its financial results for fiscal year 2020 (April 1, 2020–March 31, 2021): total revenue was 645.9 billion yen, a year-on-year decrease of 7.1%; of which, pharmaceutical business revenue was 586.1 billion yen, a year-on-year increase of 1.5%.

Japanese Pharmaceutical Business Declines; Growth Maintained in China, the US, and Europe

By region, Japan, the United States, and China rank in the top three for pharmaceutical revenue; however, Japan's revenue has declined compared to 2019.

Japan's pharmaceutical business revenue declined due to falling sales of Lyrica (pregabalin), Methycobal (mecobalamin), Aricept (donepezil), Halaven (eribulin), Pariet (rabeprazole), and Treakisym (bendamustine), with Lyrica experiencing the most significant sales drop due to generic competition. Additionally, sales of Eisai's blockbuster oncology drug Lenvima (lenvatinib) also declined in Japan, but maintained a growth trend in the United States, China, and other regions.

Growth in the pharmaceutical business in China was primarily driven by increased sales of Lenvima, Halaven, and Fycompa. Specifically, sales of Lenvima (lenvatinib) increased from JPY 13.3 billion in 2019 to JPY 18.5 billion, sales of Halaven (eribulin) grew from JPY 0.4 billion to JPY 1.6 billion, and sales of Fycompa (perampanel) rose from JPY 0.1 billion to JPY 0.5 billion.

Notably, in 2020, lenvatinib was approved in China for its second indication: radioiodine-refractory differentiated thyroid cancer, and was included in the 2020 National Reimbursement Drug List (NRDL) through price negotiations. Eribulin was approved in China in July 2019 for the treatment of locally recurrent or metastatic breast cancer in patients who had previously received at least two chemotherapy regimens (including anthracyclines and taxanes); in 2020, its sales experienced substantial growth alongside increased market penetration. Perampanel was approved in China in October 2019 as adjunctive therapy for partial-onset seizures (with or without secondary generalization) in adults and children aged 12 years and older, and was also included in the 2020 NRDL. Furthermore, in October 2020, the Center for Drug Evaluation (CDE) accepted applications for perampanel as monotherapy for partial-onset seizures and for partial-onset seizures in pediatric patients aged 4 years and older.

Lenvima Sales Continue to Rise, Aricept Sales Decline Significantly

In terms of global sales of key products, sales of most of Eisai's major products declined in 2020, with the neurological drug Aricept (donepezil) experiencing the sharpest decline.

Aricept is a second-generation centrally acting acetylcholinesterase (AChE) inhibitor. Approved by the FDA in November 1996, it became the second globally approved therapeutic drug for Alzheimer's disease (AD). It reached peak sales in 2009, and following the expiration of its patent in 2010, sales declined year by year.

Fycompa, a first-in-class antiepileptic drug developed in-house by Eisai, is a highly selective, non-competitive AMPA-type glutamate receptor antagonist. It has been approved in over 70 countries worldwide as an adjunctive therapy for the treatment of partial-onset seizures (POS, with or without secondarily generalized seizures) in patients with epilepsy aged 12 years and older, and in over 65 countries globally as an adjunctive therapy for primary generalized tonic-clonic (PGTC) seizures in patients with epilepsy aged 12 years and older. In Japan, the United States, and South Korea, it has been approved as both monotherapy and adjunctive therapy for partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy aged 4 years and older. Additionally, Fycompa has been developed for the treatment of epilepsy associated with Lennox-Gastaut syndrome.

The sales of the blockbuster anti-tumor product Lenvima/Kisplyx (lenvatinib) continue to maintain an upward trajectory, primarily driven by the expansion of its indications. Currently, Eisai and MSD are evaluating the efficacy of the Keytruda + Lenvima targeted-immunotherapy combination therapy through the LEAP (Lenvatinib and Pembrolizumab) clinical development program, which encompasses 20 clinical trials across 13 different tumor types (endometrial cancer, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, and triple-negative breast cancer).

Multiple Drugs in Development Hold Great Promise

In addition to the aforementioned products, Eisai has multiple drugs under development, such as aducanumab, lecanemab, lorcaserin, denileukin diftitox, tazemetostat, and amatuximab.

Aducanumab is the first biologic targeting the clinical decline and pathological mechanisms associated with Alzheimer's disease (AD) to be submitted to regulatory authorities for approval. It is an antibody targeting β-amyloid (Aβ) that has been demonstrated in clinical trials to clear Aβ from the brain and significantly slow the progression of mild cognitive impairment (MCI) due to AD and mild AD dementia. The drug is currently under regulatory review in Europe, the United States, and Japan. Evaluate Vantage predicts that, if successfully launched, aducanumab could achieve global sales of $4.8 billion in 2026. However, whether aducanumab will ultimately gain marketing approval remains uncertain. In January this year, the FDA extended the PDUFA target date to June 7, 2021. Subsequently, three members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee—Caleb Alexander, Scott Emerson, and Aaron Kesselheim—published an article in JAMA expressing their opposition to aducanumab.

Lecanemab is an investigational humanized monoclonal antibody for Alzheimer's disease, licensed to Eisai from BioArctic. It selectively binds to, neutralizes, and clears soluble, toxic beta-amyloid (Aβ) aggregates (protofibrils). In March 2014, Eisai and Biogen entered into a collaboration and commercialization agreement for the drug. Currently, researchers are conducting the open-label extension (OLE) study for the Phase 2 trial of lecanemab in early AD, an exploratory Phase 3 clinical trial (Clarity AD), and another Phase 3 clinical trial for preclinical AD (AHEAD 3-45).

Lorcaserin is a selective serotonin 5-HT2C receptor agonist. By selectively activating 5-HT2C receptors in the brain to activate GABAergic inhibitory interneurons, lorcaserin is expected to reduce seizures in patients with Dravet syndrome by increasing GABAergic synaptic inhibition. Currently, the Phase 3 study of lorcaserin for the indication of Dravet syndrome is ongoing, and the FDA has granted it orphan drug designation for this indication.

Denileukin diftitox (recombinant) is a fusion protein of interleukin-2 (IL-2) and the receptor-binding portion of diphtheria toxin, which specifically binds to IL-2 receptors on the surface of tumor lymphocytes. In April 2020, a marketing authorization application was submitted in Japan for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL).

Tazemetostat is an oral, first-in-class EZH2 inhibitor developed by Epizyme. EZH2 is a histone methyltransferase that, when abnormally activated, leads to the dysregulation of genes controlling cell proliferation, thereby causing uncontrolled and rapid growth of non-Hodgkin lymphoma (NHL) and various other solid tumor cells. Subsequently, Eisai entered into an agreement with Epizyme to obtain the development and commercialization rights for Tazemetostat in Japan, as well as the right of first negotiation for the drug in other Asian regions. In June 2020, the FDA approved it for the treatment of the following two indications of follicular lymphoma: ① for adult patients with relapsed or refractory follicular lymphoma harboring an EZH2 mutation who have received at least two prior systemic therapies; ② for adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.

Amatuximab is a chimeric immunoglobulin G1-kappa (IgG1/κ) monoclonal antibody with high affinity and specificity for mesothelin. Mesothelin is a glycoprotein overexpressed on the surface of mesothelioma cells. In January 2014, it was granted orphan drug designation by the EC for the treatment of malignant mesothelioma.