Nerandomilast Secures EU Nod, But Incremental Efficacy and Evidence Gaps Create a Vulnerable First-Mover Position

European Commission Approves JASCAYD for IPF and PPF

The European Commission has granted marketing authorization for Boehringer Ingelheim's JASCAYD® (nerandomilast), an oral, preferential PDE4B inhibitor, for adults with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) in the EU. This approval marks the first new treatment for IPF in over a decade and for PPF in over five years. The decision is based on the Phase III FIBRONEER™ program, which demonstrated that nerandomilast effectively slows lung function decline, measured by forced vital capacity (FVC), and exhibited a favorable safety and tolerability profile with monotherapy discontinuation rates similar to placebo.

• JASCAYD® (nerandomilast) is the first oral, preferential phosphodiesterase 4B (PDE4B) inhibitor approved in the EU, offering a novel mechanism of action with antifibrotic and immunomodulatory effects. This approval addresses a significant unmet medical need for patients with IPF and PPF, conditions characterized by irreversible lung scarring, providing a new treatment option after a long hiatus in the EU.
• The EC approval is supported by the Phase III FIBRONEER™ program, the largest clinical trial conducted in IPF and PPF to date. In both FIBRONEER™-IPF and FIBRONEER™-ILD trials, nerandomilast successfully met its primary endpoint by significantly slowing lung function decline, as measured by the absolute change in forced vital capacity (FVC) from baseline to week 52, compared to placebo.
• Nerandomilast demonstrated a favorable safety and tolerability profile in clinical trials, notably showing monotherapy discontinuation rates similar to placebo. This is a crucial advancement, as existing therapies often lead to early discontinuation due to side effects. Furthermore, the drug requires no liver monitoring, reducing patient burden and potentially improving long-term adherence.

Nerandomilast's Favorable Safety and Efficacy Profile in FIBRONEER™

Nerandomilast has demonstrated a favorable safety and tolerability profile in patients with fibrotic lung diseases, as evidenced by low discontinuation rates in the FIBRONEER™ clinical trial program. In the FIBRONEER-IPF trial for idiopathic pulmonary fibrosis, adverse events (AEs) led to treatment discontinuation in 13.5% of patients receiving nerandomilast 9 mg bid and 16.1% receiving 18 mg bid, which was comparable to the 13.0% rate in the placebo arm. Similarly, in the FIBRONEER-ILD trial for progressive pulmonary fibrosis, discontinuation rates were 12.0% (9 mg bid) and 12.3% (18 mg bid) versus 12.5% for placebo. This consistent tolerability was observed over a substantial mean treatment exposure of approximately 15 months across both studies. Notably, in a subgroup of patients with autoimmune disease-related ILD, discontinuation rates in the nerandomilast arms were even lower, at 8.0% and 10.6% for the 9 mg and 18 mg doses, respectively.

The most common AE associated with nerandomilast treatment was diarrhea, which was reported more frequently than with placebo but was generally described as mild and manageable. Other reported AEs included nausea and mild fatigue. Importantly, the incidence of serious adverse events (SAEs) was similar across all treatment and placebo groups. A meta-analysis reinforces this safety profile, indicating that nerandomilast did not increase the relative risk of overall AEs (RR: 1.00, 95% CI: 0.98-1.02) or SAEs (RR: 0.93, 95% CI: 0.76-1.14) when compared to placebo. Furthermore, the favorable tolerability of nerandomilast was maintained in patients receiving it both as monotherapy and in combination with background nintedanib therapy.