Boehringer Ingelheim’s Jascayd (nerandomilast) receives approval from Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of adults with idiopathic pulmonary fibrosis (IPF) and adults with progressive pulmonary fibrosis (PPF), making Japan the fourth market to authorize the drug following the US, China, and the United Arab Emirates. The decision introduces the first oral PDE4B inhibitor approved in these indications and, in IPF specifically, the first new treatment option in more than a decade.
The MHLW approval covers nerandomilast as an oral therapy for both IPF and PPF in adults, with no line-of-therapy restriction stated. The drug acts by selectively inhibiting phosphodiesterase 4B, an enzyme involved in the degradation of cyclic AMP, thereby modulating downstream antifibrotic and immunomodulatory signaling in the lung. This dual mechanism distinguishes nerandomilast from the two established oral antifibrotics — nintedanib (Ofev), a multi-tyrosine kinase inhibitor, and pirfenidone (Esbriet), a TGF-β modulator — both approved for IPF since 2014, with nintedanib also approved for PPF.
The approval is supported by data from the Phase III FIBRONEER-IPF and FIBRONEER-ILD trials, described by Boehringer Ingelheim as the largest Phase III program conducted across IPF and PPF to date. In FIBRONEER-IPF, nerandomilast met its primary endpoint, with the 18 mg dose demonstrating a 68.8 mL difference versus placebo in absolute change in forced vital capacity (FVC) from baseline to week 52. In FIBRONEER-ILD, the 9 mg dose produced an 81.1 mL difference versus placebo on the same measure, with both doses achieving statistical significance. Neither trial met its key secondary composite endpoint, which combined acute exacerbation, first hospitalization for respiratory cause, and death. A pooled analysis of both trials reported a 59% reduction in the risk of death in the nerandomilast 18 mg group without existing background treatment compared with placebo, though this result was described as nominally significant.
The most commonly observed adverse event across both trials was diarrhea, reported in 41.3% of patients receiving nerandomilast 18 mg in FIBRONEER-IPF versus 16.0% in the placebo group. Discontinuation rates due to adverse reactions in that trial were 14.0% for the 18 mg group and 10.7% for placebo. The tolerability profile is relevant in the Japanese context: the company noted that approximately one-third of patients in Japan do not initiate antifibrotic therapy due to concerns about gastrointestinal and hepatic side effects, particularly among older adults.