Japan Approved a New ALS Drug in 2024. The FDA Still Hasn't.

Amyotrophic lateral sclerosis moves quickly, and the list of drugs that can slow it is short. For years it held essentially two names that most neurologists reached for. In September 2024, Japan added another — a purified, ultra-high-dose form of vitamin B12. In the United States, that option is still not on the shelf.

The drug is mecobalamin (also called methylcobalamin), marketed in Japan by Eisai as Rozebalamin. It is the same B12 compound sold cheaply over the counter, but at a dose and purity that make it a prescription medicine rather than a supplement, and the evidence behind its approval came from a carefully run trial rather than folklore about vitamins.

How it works

The approved regimen is 50 mg injected into muscle twice a week — roughly ten thousand times a typical daily oral B12 dose. Researchers believe the benefit comes partly from lowering homocysteine, an amino acid that builds up when B12-dependent pathways run short and that appears to be toxic to motor neurons. Laboratory work also points to a possible role in protecting nerve axons and supporting their repair. The precise mechanism is still not fully understood, which the Japanese label acknowledges.

Where each country stands

Japan’s Ministry of Health, Labour and Welfare approved Rozebalamin on September 24, 2024, and Eisai launched it that November. The approval is deliberately narrow: it covers people in the early stage of ALS, within about one year of symptom onset, who are showing moderate progression.

That specificity comes from the trial history. An earlier Japanese phase 2/3 study of about 370 patients, run in the mid-2000s, failed to show a benefit across the whole ALS population. But a closer look suggested that patients treated early, at the higher dose, declined more slowly. Researchers designed a confirmatory trial around exactly that group. The JETALS study — a multicenter, placebo-controlled, double-blind phase 3 trial of roughly 130 patients, funded by the Japan Agency for Medical Research and Development and published in JAMA Neurology in 2022 — met its primary goal. Over 16 weeks, the mecobalamin group’s score on the standard ALS function scale (ALSFRS-R) fell by 2.66 points versus 4.63 points on placebo, a difference of about 1.97 points (P = 0.01), or roughly a 43% slower rate of functional decline. A follow-on open-label extension reported no new safety concerns over 52 weeks.

In the United States, there is no FDA-approved ultra-high-dose mecobalamin for ALS, and none anywhere outside Japan. American neurologists work with riluzole, edaravone, and the SOD1-specific drug tofersen for the small subset of patients who qualify. A U.S. patient who wants Rozebalamin generally has to pursue personal import or named-patient access with their physician — a slower, costlier, and less certain path than a prescription filled at a local pharmacy.

Why this gap exists

This is not a case of American medicine lagging. The U.S. approved tofersen, the first gene-targeted ALS therapy, ahead of most of the world, and it remains a leader in ALS genetics and trial infrastructure. The difference is one of regulatory judgment and geography: JETALS was a Japanese trial, funded by a Japanese agency, submitted to a Japanese regulator that was willing to approve a modest but real benefit in a well-defined early group. There is precedent for the crossing eventually happening — edaravone, now sold in the U.S. as Radicava, was approved in Japan in 2015 and reached American patients about two years later.

The thread back to timing

JETALS carries a lesson that reaches beyond one drug: the benefit showed up only in patients treated early. In a disease measured in months, the window to act is narrow, and it closes before many people even have a diagnosis. That is the same principle behind Japan’s Ningen Dock screening culture — that the value of a medical finding depends heavily on how early it is made. For most conditions, the stakes are less stark than in ALS, but the direction of the lesson is the same.

Sources: Eisai: Rozebalamin approved in Japan for ALS; Eisai: Rozebalamin launched in Japan; Oki R, et al. “Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial,” JAMA Neurology, 2022 (PubMed); JETALS protocol, JMIR Research Protocols, 2018; ALS News Today: High-dose B12 slows functional decline in early-stage ALS; International Alliance of ALS/MND Associations: Rozebalamin / Methylcobalamin; ClinicalTrials.gov NCT03548311