P135 Efficacy and safety of nerandomilast in patients with autoimmune disease-related progressive pulmonary fibrosis: subgroup analysis of the FIBRONEER-ILD trial

Abstract Background/Aims Nerandomilast is a preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory properties. The Phase III FIBRONEER-ILD trial in patients with progressive pulmonary fibrosis (PPF) showed that nerandomilast significantly reduced the decline in forced vital capacity (FVC) and had an acceptable safety profile. We explored the efficacy and safety of nerandomilast in the subgroup of patients with autoimmune disease-related interstitial lung diseases (ILDs) (autoimmune ILDs) in the FIBRONEER-ILD trial. Methods Patients with PPF (excluding idiopathic pulmonary fibrosis) were randomized 1:1:1 to receive nerandomilast 9 mg bid, nerandomilast 18 mg bid, or placebo. PPF was defined using the same criteria as in the INBUILD trial. Patients taking nintedanib (at a stable dose for ≥12 weeks) or not taking nintedanib (for ≥8 weeks) were eligible to participate. Cyclophosphamide, tocilizumab, mycophenolate, or rituximab were not permitted at enrolment but could be initiated after 6 months to manage worsening systemic disease. Prednisone 15 mg/day (or equivalent) was not permitted at enrolment but could be prescribed during the trial for acute exacerbation of ILD or after 6 months to manage worsening systemic disease. In the subgroup with autoimmune ILDs, we evaluated absolute change from baseline in FVC (mL) at week 52 and adverse events up to week 52. Analyses were pre-specified. Results Among 1176 treated patients, 325 (27.6%) had autoimmune ILDs (100 placebo, 112 nerandomilast 9 mg bid, 113 nerandomilast 18 mg bid). At baseline, among patients with autoimmune ILDs, 212 (65.2%) were female, mean (SD) age was 63.4 (11.2) years, FVC was 71.5 (15.0) % predicted, diffusing capacity for carbon monoxide (DLco) was 51.5 (16.8) % predicted; 111 (34.2%) patients were taking nintedanib. The most frequent autoimmune disease diagnoses were rheumatoid arthritis (118 patients 36.3%), systemic sclerosis (75 23.1%), and mixed connective tissue disease (47 14.5%). Among patients with autoimmune ILDs, adjusted mean changes in FVC (mL) at week 52 were -107.1 (95% CI: -156.1, -58.0) in the placebo group, -61.2 (-106.9, -15.5) in the nerandomilast 9 mg bid group (difference vs placebo: 45.9 95% CI: -20.8, 112.6), and -64.9 (-111.0, -18.7) in the nerandomilast 18 mg bid group (difference vs placebo: 42.2 -24.9, 109.3). The most frequent adverse event was diarrhea. Adverse events leading to treatment discontinuation were similar across treatment groups. Conclusion In the FIBRONEER-ILD trial, the efficacy of nerandomilast on slowing decline in FVC in patients with autoimmune ILDs was consistent with that observed in the overall trial population. Nerandomilast had an acceptable safety and tolerability profile. Disclosure A. Hoffman-Vold: Consultancies; Boehringer Ingelheim, AbbVie, Avalyn, Bristol Myers Squibb, Calluna Pharma, Genentech, Janssen, Medscape, Merck Sharp Boehringer Ingelheim, Janssen, Medscape, Merck Sharp Boehringer Ingelheim, Janssen. S. Assassi: Consultancies; Boehringer Ingelheim, AbbVie, AstraZeneca, aTyr, CSL Behring, Mitsubishi Tanabe, Merck Sharp aTyr, Boehringer Ingelheim, Janssen. V. Cottin: Consultancies; AbbVie, AstraZeneca, Avalyn, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CSL Vifor, Ferrer/United Therapeutics, Gossamer, GlaxoSmithKline, Liquidia, Pliant, PureTech, Roche, Roivant, Sanofi, Shionogi. Honoraria; Boehringer Ingelheim, Ferrer/United Therapeutics, Roche, Sanofi. Other; GlaxoSmithKline, Molecure, FibroGen. M. Kreuter: Corporate appointments; Deutsche Gesellschaft für Pneumologiex, European Respiratory Society. Consultancies; AstraZeneca, Avalyn, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Pliant, Roche. Honoraria; Boehringer Ingelheim, Roche. Grants/research support; Boehringer Ingelheim, Roche. C. Valenzuela: Consultancies; Boehringer Ingelheim, Bristol Myers Squibb, Ferrer, Pliant, Roche. Other; Boehringer Ingelheim, Pliant, Roche, Ferrer. M.S. Wijsenbeek: Corporate appointments; Dutch Lung Fibrosis and Sarcoidosis Patient Associatiations. Consultancies; AstraZeneca, Avalyn, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Galapagos, Galecto, GlaxoSmithKline, Hoffman-La Roche, Horizon Therapeutics, Kinevant Sciences, Molecure, NeRRe Therapeutics, Novartis, PureTech Health, Trevi, Vicore. Honoraria; Avalyn, Boehringer Ingelheim, CSL Behring, Novartis, Sanofi. Grants/research support; AstraZeneca/Daiichi Sankyo, Boehringer Ingelheim, Hoffman-La Roche, Sarcoidosis.nl, The Dutch Lung Foundation, The Dutch Pulmonary Fibrosis Patients Association, The Netherlands Organization for Health Research and Development, The Thorax Foundation. Other; European Respiratory Society, Boehringer Ingelheim, GlaxoSmithKline, Hoffman-La Roche. H. Gu: Corporate appointments; Boehringer Ingelheim. I. Ritter: Corporate appointments; Boehringer Ingelheim. S. Stowasser: Corporate appointments; Boehringer Ingelheim. G. Weimann: Corporate appointments; Boehringer Ingelheim. T. Maher: Consultancies; AbbVie, Amgen, AstraZeneca, Bayer, Biogen, Blade Therapeutics, Bristol Myers Squibb, Boehringer Ingelheim, Endeavour BioMedicines, Galapagos, Galecto, GlaxoSmithKline, Gossamer Bio, Merck, Pfizer, Pliant, Roche, Redx Pharma, Trevi Pharma, Three Lakes Partners, UCB, United Therapeutics, Vicore Pharma. Honoraria; Boehringer Ingelheim, Roche. Grants/research support; AstraZeneca, GlaxoSmithKline, UCB.