Unlocking Japan’s Potential in Rare Disease Drug Development: Recent Progress and Challenges (2025)

Japan has recently designated several innovative therapies as orphan drugs, signaling increased regulatory support for rare disease drug development.

On June 27, 2025, Tamibarotene received orphan drug designation from Japan's Ministry of Health, Labour and Welfare (MHLW) for treating Autosomal Dominant Polycystic Kidney Disease (ADPKD), and is currently in Phase 2a clinical trials targeting Japanese patients with plans for global development1.

Riliprubart, a monoclonal antibody for chronic inflammatory demyelinating polyneuropathy (CIDP), was granted Japan orphan drug status in June 2025, highlighting alignment between Japanese and Western regulatory agencies in addressing global unmet needs5.

JR-446, a therapy for the ultra-rare Sanfilippo syndrome type B (MPS IIIB), received Japanese orphan drug designation in 2025, following similar approvals in the US and Europe, illustrating Japan's engagement in global drug innovation for ultra-rare diseases7.

Despite these advances, Japan faces a growing 'orphan drug lag,' with a widening gap between drugs approved in the US/Europe and those available in Japan since 2017. This lag is especially pronounced for rare diseases due to shifts in R&D strategies and the rise of US/EU-based small- to mid-sized enterprises (SMEs) that often lack Japanese market entry2 3.

Efforts to address this lag include regulatory reforms, such as not requiring extra phase 1 trials in Japanese subjects if global safety data is robust, and incentives to attract foreign innovation13. However, foreign SMEs remain unlikely to enter Japan independently, making proactive global partnerships by Japanese companies essential to enable timely access to novel therapies2 3 13.

Building a robust drug discovery ecosystem and earlier in-licensing of promising drug candidates from international SMEs are priority recommendations for Japan to fulfill unmet rare disease needs and unlock the country's innovation potential2 3.