THU402 New Heterotopic Ossification Lesions In Patients With Fibrodysplasia Ossificans Progressiva Measured By PET/CT vs CT Only

Disclosure: D. Gonzalez Trotter: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. J. McGinniss: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. A.N. Economides: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. K. Mohammadi: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. A.J. Rankin: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. B. Musser: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. S. Mellis: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. E. Forleo-Neto: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. G. Herman: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder caused by mutations in the activin-A receptor type 1 (ACVR1) gene that render it responsive to activin-A, a ligand that normally antagonizes signaling from ACVR1. FOP is characterized by the deposition of bone in soft tissues known as heterotopic ossification (HO) and episodic painful flare-ups. Garetosmab, a fully human monoclonal antibody against activin-A, is being investigated for the prevention of new HO lesions in patients with FOP. This post hoc analysis compared the change from baseline in the number and volume of new HO lesions identified by (18)F-labeled sodium fluoride (a bone-seeking tracer that measures bone deposition and turnover) positron emission tomography (PET/CT) and X-ray computed tomography (CT) imaging (which measures bone volume). Methods: Baseline and 28-week PET/CT and CT-only scans acquired during the initial double-blind placebo-controlled period of the LUMINA-1 (NCT03188666) phase 2 study were independently read by two sets of blinded readers and an adjudicator for the presence and volume of new lesions. Number and volume of new lesions were compared between the two imaging modalities. Results: The number of patients with new lesions as detected by PET/CT and CT only was 14/44 (31.8%) and 12/44 (27.3%), respectively. The mean number (standard deviation) of new lesions per patient by PET/CT through Week 28 was 0.68 (1.57) vs 0.86 (1.95) as detected by CT only. In patients with new lesions, the mean number of new lesions per patient was 2.14 (2.18) vs 3.17 (2.62) as detected by PET/CT vs CT only, respectively. The mean volume (cm(3)) of new lesions per patient detected by PET/CT was 6.05 (14.88) vs 5.94 (21.13) by CT only, through Week 28. In the subset of patients with new lesions, the mean volume of new lesions per patient detected by PET/CT was 19.02 (21.60) vs 21.79 (36.98) by CT only. Moderate agreement between PET/CT and CT-only detection was observed when identifying patients with new lesions, with a kappa coefficient of 0.46 (standard error: 0.146; 95% confidence interval: 0.17, 0.74). Placebo vs garetosmab groups, respectively, showed aggregate new lesion number/volume (cm(3)) of 27/245.0 vs 3/21.3 by PET/CT, and 37/261.5 vs 1/0.05 by CT only. Conclusions: CT imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions and provides a viable option for the assessment of therapies that may inhibit the formation of new HO lesions in patients with FOP. Presentation: Thursday, June 15, 2023