NDA submitted in Japan for mecobalamin ultra high dose formulation to treat amyotrophic lateral sclerosis

In May 2022, ultrahigh-dose mecobalamin received orphan drug designation by the Ministry of Health, 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 investigator initiated 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 and weakness 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 within approximately 3 to 6 years from the onset of the disease. The number of patients in Japan is estimated to be 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.

See- "Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis A Randomized Clinical Trial"- Ryosuke Oki, MD; Yuishin Izumi, MD, PhD; Koji Fujita, MD, PhD; et al JAMA Neurol. 2022; doi: 10.1001/jamaneurol.2022.0901

See-MIR Res Protoc. 2018 Dec 21;7(12):e12046. doi: 10.2196/12046.."The Japanese Early-Stage Trial of High-Dose Methylcobalamin for Amyotrophic Lateral Sclerosis (JETALS): Protocol for a Randomized Controlled Trial."- Ryosuke Oki , Yuishin Izumi , Hiroyuki Nodera , Yasutaka Sato , Hiroshi Nokihara , Kazuaki Kanai , Masahiro Sonoo , Makoto Urushitani, Kazuto Nishinaka , Naoki Atsuta , et al., PMID: 30578206 PMCID: PMC6320396 DOI: 10.2196/12046.