Late Breaking Abstract - Evaluating the feasibility, safety, and efficacy of senolytics in idiopathic pulmonary fibrosis

Cellular senescence is a key mechanism that drives age-related diseases such as idiopathic pulmonary fibrosis (IPF). Selective ablation of senescent cells using dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction in bleomycin-administered mice. A two-stage clinical study in patients with stable IPF was conducted to evaluate feasibility of implementing intermittent DQ (D:100mg/day, Q:1250mg/day, 3-d/wk over 3-wks). First, an open-label study (OL) was performed at two clinical sites followed by a single-site double-blind randomized placebo-controlled trial (RCT; ongoing). The primary endpoints were retention and completion rates for planned assessments. Secondary endpoints were safety and change in functional and reported health measures. Associations with the senescence-associated secretory phenotype (SASP) were explored. 14 patients were recruited in the OL study and 12 in the RCT. Retention rate was 100%; planned assessments were complete in 25/26. Two serious adverse events were reported; one unrelated. Non-serious adverse events were primarily mild-moderate but none led to premature discontinuation or withdrawal. In the OL study, physical function assessments, as measured by 6-min walk, 4-m gait speed, and chair-stands time, were all significantly and meaningfully improved (p<0.05). Functional and reported health measures were unchanged. Although DQ effects on circulating SASP factors were inconclusive, improved physical function correlated with reduced SASP-related factors (23/48 markers, r≥0.50). RCT analyses pending. This two-stage clinical study supports trial feasibility and safety of DQ in IPF patients. Larger future RCTs to assess safety & efficacy should be pursued.