Tvardi says benefit of TTI-101 treatment not observed in REVERT trial

Tvardi Therapeutics (TVRD) provided an update on preliminary data from the Phase 2 REVERT clinical trial of TTI-101 in idiopathic pulmonary fibrosis. Overall, 88 patients were randomized to TTI-101 400mg per day, 800mg per day or placebo and stratified by nintedanib use, with 58% of patients receiving concomitant therapy. Preliminary data demonstrated patients’ baseline characteristics were similar across treatment arms, with the exception of percent predicted FVC, which was lower in the placebo-treated patients compared to the TTI-101-treated arms. Discontinuation rates across treatment arms were imbalanced, with lower discontinuation rates observed in the placebo group compared to treated arms. Discontinuation rates among the TTI-101 population were primarily driven by gastrointestinal adverse events, with higher rates of events and discontinuations among patients on concurrent nintedanib. The study was not powered to evaluate exploratory endpoints. The number of efficacy evaluable patients with at least one baseline and on-treatment FVC measurement was placebo, 400mg, and 800mg. The numbers, however, declined by the 12-week timepoint to placebo, 400mg, or 800mg. The preliminary analysis was performed on actual FVC values; values were not modeled or imputed. Preliminary analysis of exploratory efficacy showed no statistically significant differences between placebo and treatment arms. Overall, from baseline to last visit on treatment, the proportion of patients who demonstrated FVC improvement from baseline was 41% for the placebo, and 39% and 44% for the 400mg and 800mg arms, respectively. FVC change from baseline overlapped between treatment arms, with large variability within each cohort. Notably, the placebo-treated patients’ FVC decline was lower than expected compared to historical controls. Imran Alibhai, CEO of Tvardi, stated, “In the aggregate, we did not observe a benefit of TTI-101 treatment in this IPF study. The limited data set, high variability within treatment arms, and unexpected performance of the placebo arm make it difficult to provide more definitive conclusions at this time. We are conducting additional analyses to further understand the results and inform our next steps. I want to sincerely thank the patients, their families, investigators, and site staff for their commitment to this study.”