Abstract Rationale Idiopathic pulmonary fibrosis (IPF) causes progressive loss of lung function and there is an unmet need for antifibrotic treatment that offers enhanced efficacy versus currently approved antifibrotics. Deupirfenidone (DPF) is a strategically deuterated form of pirfenidone that retains its pharmacodynamic activity but has a differentiated pharmacokinetic profile that may enable improved efficacy and favorable tolerability. A phase 2b trial in IPF demonstrated that DPF 825 mg three times a day (TID) had a statistically significant effect on the primary outcome measure of change in 26-week forced vital capacity (FVC) compared with placebo and resulted in a numeric improvement versus pirfenidone NCT05321420. Consequently, deupirfenidone is being assessed in a pivotal phase 3 study in patients with IPF (SURPASS-IPF). Methods SURPASS-IPF is a phase 3, international, double-blind, randomized, active comparator trial. Approximately 1100 patients will be randomized 1:1 to either deupirfenidone 825 mg TID or pirfenidone 801 mg TID for at least 52 weeks. Eligible patients will have a diagnosis of IPF per international guidelines confirmed through central review of high-resolution chest CT along with an FVC percent of predicted (FVCpp) ≥45%. Concurrent antifibrotic therapy will not be allowed, however, prior exposure of 1 year to approved antifibrotics other than pirfenidone will be allowed. Patients will remain on blinded study drug until the last patient completes 52 weeks. An optional open label extension study is planned. The study is powered to demonstrate superiority of DPF over pirfenidone in the primary endpoint of absolute change in FVC (mL) from baseline to week 52. Secondary endpoints include time to clinical worsening (first event of death, non-elective respiratory hospitalization or 10% decline in FVCpp), time to first acute exacerbation of IPF, overall survival, and change in the Living with Pulmonary Fibrosis (L-PF) Questionnaire at week 52 and at completion of the blinded trial. Safety and tolerability parameters including adverse events, laboratory parameters, and dose modifications will be monitored. Conclusion SURPASS-IPF is the first phase 3 head-to-head study comparing an investigational drug to an approved antifibrotic in patients with IPF. Deupirfenidone 825 mg TID has already demonstrated superiority to placebo and a direct comparison to pirfenidone will allow clinicians and patients living with IPF to assess its safety and efficacy. This abstract is funded by: PureTech Health
Maher et al. (Fri,) studied this question.