Eisai Co., Ltd. has announced the launch of Rozebalamin® for Injection 25 mg (mecobalamin) in Japan, a new treatment option aimed at slowing the progression of functional impairment in patients with amyotrophic lateral sclerosis (ALS). The launch follows its approval on September 24, 2024, and subsequent inclusion in Japan’s National Health Insurance Drug Price List.
The approval of Rozebalamin is primarily based on the results of the Japan Early-Stage Trial of Ultrahigh-Dose Methylcobalamin for ALS (JETALS), a Phase III clinical trial. This multicenter, placebo-controlled, double-blind, randomized study involved 130 patients with ALS and was initiated by researchers from Tokushima University and Chiba University.
Clinical Efficacy and Trial Data
The JETALS trial demonstrated a statistically significant difference in the change in ALSFRS-R total score, the primary endpoint, between the mecobalamin and placebo groups. Patients receiving mecobalamin 50 mg showed a change of -2.7 [95% CI: -3.9, -1.5], while the placebo group experienced a change of -4.6 [95% CI: -5.8, -3.4]. The difference in change was 2.0 (95% CI: 0.4, 3.5; p=0.012), indicating the superiority of mecobalamin over placebo in slowing functional decline.
The trial included patients who had been diagnosed with ALS for less than one year, classified as “definite,” “probable,” or “probable-laboratory supported” according to the Updated Awaji Criteria. Participants also had an ALS severity rating of grade 1 or 2, a decrease of 1 or 2 points in the ALSFRS-R total score 12 weeks prior to administration, and a forced vital capacity (%FVC) of more than 60%.
Dosage, Administration, and Safety
The recommended dosage of Rozebalamin is 50 mg administered intramuscularly twice a week. The adverse drug reaction incidence rate in the mecobalamin group was 7.7% (5/65 cases), with observed reactions including constipation, injection site pain, fever, electrocardiogram QT prolongation, and rash. In comparison, the placebo group had an adverse drug reaction incidence rate of 1.6% (1/64 cases).
Addressing Unmet Needs in ALS Treatment
ALS is a progressive neurodegenerative disease characterized by muscle atrophy and weakness due to motor neuron dysfunction. The condition leads to respiratory failure and typically results in death within 2 to 5 years from onset without artificial respiratory support. In Japan, approximately 10,000 individuals are affected by ALS. Given the limited number of approved treatments, Rozebalamin represents a significant advancement in addressing the unmet medical needs of ALS patients.
Mecobalamin's Mechanism of Action
Mecobalamin is already approved as Methycobal for treating peripheral neuropathies and megaloblastic anemia caused by vitamin B12 deficiency. While the precise mechanism of action of mecobalamin in ALS is not fully understood, non-clinical research suggests it may exert neuroprotective effects and promote nerve axon regeneration. Ultrahigh-dose mecobalamin, at 50 to 100 times the approved dosage of Methycobal, has shown potential clinical benefits in ALS, leading to Eisai's Phase II/III clinical trial (Study 761) and subsequent development of Rozebalamin.
Regulatory Context
Rozebalamin received orphan drug designation from the Japanese Ministry of Health, Labour and Welfare in May 2022, underscoring its importance in treating this rare and debilitating disease.
