Development of guidelines for ALS clinical trials

Abstract

The revised ALS clinical practice guidelines were published for the first time in a decade in 2023, emphasizing pharmacological treatment, particularly riluzole and edaravone, supported by accumulating evidence. However, Japan faces a growing concern over “drug loss,” where innovative therapies developed abroad fail to reach domestic markets due to high clinical trial costs and low drug pricing.

ALS drug development has accelerated globally, with over 50 clinical trials in progress. North American and European consortia, such as NEALS, ENCALS, and TRICALS, have adopted adaptive and platform trials to streamline drug approval. Japan, however, remains largely excluded from these global trials.

Despite the success of Japan's JaCALS registry and significant contributions to ALS research, only two out of 11 ongoing phase III trials include Japan. Additionally, 143 drugs approved overseas remain unavailable in Japan, with 86 yet to be pursued domestically. To address this, the ALS Clinical Trial Project Team (ACT–PT) is conducting feasibility studies to enhance trial participation.

Establishing ALS clinical trial guidelines and fostering international collaboration are crucial to mitigating Japan's drug loss and promoting domestic drug development. By integrating global trial networks, Japan aims to improve access to cutting–edge ALS treatments.