新薬登場後のALS治験

抄録

In 2024, two new drugs for amyotrophic lateral sclerosis (ALS)―mecobalamin and tofersen―were approved in Japan, increasing the total number of available ALS therapies to four, the highest worldwide. Despite these advances no curative treatment has been established, and clinical trials remain essential. However, Japan's participation in global phase III trials remain limited, raising concerns about future drug lag.

The emergence of new therapies has important implications for clinical trial design. When planning trials in the presence of existing treatments, clear criteria for concomitant medication use are required. While allowing concomitant use of approved drugs may reflect real–world practice, it can complicate efficacy evaluation. Conversely, restricting concomitant medications may negatively affect patient recruitment. In addition, as the efficacy of mecobalamin has been demonstrated in patients within one year of disease onset, some patients may prioritize its use over trial participation depending on disease stage.

Tofersen, an antisense oligonucleotide targeting superoxide dismutase 1 (SOD1), is indicated only for SOD1–ALS. Therefore, it is unlikely to affect trials targeting sporadic ALS or other genetic forms. However, in trials focusing on SOD1–ALS, concomitant use of tofersen in likely to be restricted, particularly in studies involving nucleic acid–based therapeutics.

To facilitate timely approval of promising therapies, both drug development and clinical trial infrastructure must be strengthened. Since 2024, we have been conducting an AMED–funded project to develop clinical evaluation guidelines for ALS therapeutics. In parallel, a nationwide questionnaire survey conducted in 2025 assessed the readiness of Japanese institutions to participate in ALS clinical trials. These efforts aim to promote efficient trial implementation and enhance Japan's contribution to global ALS drug development.