A phase 2b randomized trial to evaluate LYT-100 in patients with idiopathic pulmonary fibrosis (IPF)

Rationale: Pirfenidone and nintedanib are approved for IPF treatment worldwide but can cause significant tolerability issues, leading to treatment discontinuation and/or dose reductions. LYT-100, a selectively deuterated form of pirfenidone, is expected to retain the anti-fibrotic and anti-inflammatory activity of pirfenidone at comparable daily exposures but with lower dose levels. Completed Phase 1 studies suggest LYT-100 may be better tolerated than pirfenidone, with lower Cmax but comparable overall exposure (AUC) as pirfenidone. Design: A 260 patient multicenter, randomized, double-blind trial to compare the efficacy, tolerability, and safety of two doses of LYT-100 (550 and 825 mg TID) to both placebo and pirfenidone 801mg TID. The primary endpoint will be forced vital capacity (FVC) decline over 26 weeks in adult patients with IPF who are treatment naïve. The primary objectives are to determine the optimal dosing regimen of LYT-100 and to describe the benefit-risk profile of LYT-100 vs pirfenidone. Conclusions: LYT-100 has the potential to address a significant unmet need for IPF patients by offering a more tolerable treatment option than current antifibrotics. This trial will compare LYT-100 to an existing SOC and placebo and aims to demonstrate both efficacy and tolerability. The study may lead to a more straightforward regulatory pathway for deuterated pirfenidone for treatment of IPF.