No.24-08

January 26, 2024
Eisai Co., Ltd.

EISAI SUBMITS NEW DRUG APPLICATION FORMECOBALAMIN ULTRAHIGH-DOSE FORMULATION IN JAPAN FOR
THE INDICATION OF AMYOTROPHIC LATERAL SCLEROSIS

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has submitted a
New Drug Application (NDA) for ultrahigh-dose mecobalamin (development code: E0302) for the indicationof amyotrophic lateral sclerosis (ALS) to the Pharmaceuticals and Medical Devices Agency (PDMA) inJapan. In May 2022, ultrahigh-dose mecobalamin received orphan drug designation by the Ministry ofHealth, Labour and Welfare (MHLW).
This application is based on the results of JETALS (The Japan Early-Stage Trial of Ultrahigh-Dose
Methylcobalamin for ALS), a Phase III trial to evaluate efficacy and safety of ultrahigh-dose
methylcobalamin (mecobalamin) in early onset ALS patients, that was conducted as an investigatorinitiated trial by a research team with Extraordinary Professor Ryuji Kaji (Principal Investigator), Tokushima
University, and Professor Yuishin Izumi (Coordinating Investigator), the Department of Neurology,Tokushima University Graduate School of Biomedical Sciences, and Professor Satoshi Kuwabara(Coordinating Investigator), the Department of Neurology, Chiba University Graduate School of Medicine.
The results of JETALS were published in the peer-reviewed journal JAMA Neurology.
ALS is an intractable, progressive, neurodegenerative disease that results in severe muscle atrophy andweakness in the muscles due to motor neuron dysfunction. As the main cause of death is respiratory failure
due to paralysis of the respiratory muscles, without the use of an artificial respirator, death occurs withinapproximately 3 to 6 years from the onset of the disease. The number of patients in Japan is estimated tobe approximately 10,000. Currently, there is no curative treatment established for ALS, and since there
are only limited number of medicines approved in Japan and abroad, this is a disease with significant
unmet medical needs.
Eisai considers neurology a therapeutic area of focus. As a human healthcare company, Eisai is committed
to fulfill unmet medical needs in neurology and further its contribution to improving the benefit of patientsand the people in the daily living domain.

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

[Notes to editors]
1.

About Mecobalamin
Mecobalamin (generic name, development code: E0302) is approved and marketed as Methycobal®, a 500 µg
injection of mecobalamin indicated for the treatment of peripheral neuropathies and megaloblastic anemia
caused by vitamin B12 deficiency. Methycobal is also approved as a tablet formulation (250µg and 500 µg) as
well as a fine granule formulation (0.1%) indicated for the treatment of peripheral neuropathies. While themechanism of action of mecobalamin in amyotrophic lateral sclerosis (ALS) is not known, it has been suggested
in non-clinical research that mecobalamin may have efficacy through a neuroprotective effect and regenerationof nerve axons. Since the 1990s, clinical research has been carried out on ultrahigh-dose mecobalamin in ALS
by a study group on neurodegenerative disease, funded through the Ministry of Health, Labour and Welfare's
Specified Disease Treatment Research Program. Short- and long-term trials of intramuscular injection ofmecobalamin at 25 mg and 50 mg per day, which is respectively 50 and 100 times the approved dosage ofMethycobal, suggested that ultrahigh-dose mecobalamin could have a clinical effect in ALS. Therefore, Eisai
had conducted the Phase II/III clinical trial (Study 761) since 2006 and submitted a new drug application for
ultrahigh-dose mecobalamin as treatment for ALS in May 2015 but withdrew the application in March 2016 after
the Pharmaceuticals and Medical Devices Agency (PMDA) indicated that additional clinical trials werenecessary.
Following favorable clinical trial results in JETALS, Eisai prepared to file a new drug application for ALS in Japan.