Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP): Results of a Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial

J Bone Miner Res. 2022 Jul 19. doi: 10.1002/jbmr.4655. Online ahead of print.ABSTRACTFibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO), often heralded by flare-ups, leading to reduced movement and life expectancy. This placebo-controlled, double-blind trial (NCT02190747) evaluated palovarotene, an orally bioavailable selective retinoic acid receptor gamma agonist, for prevention of HO in patients with FOP. Patients experiencing a flare-up were enrolled in two cohorts: 1) patients ≥15 years were randomized 3:1 to palovarotene 10/5 mg (Weeks 1-2/3-6) or placebo; 2) patients ≥6 years were randomized 3:3:2 to palovarotene 10/5 mg, palovarotene 5/2.5 mg (Weeks 1-2/3-6), or placebo. Cohort data were pooled. The primary endpoint was the proportion of responders (no/minimal new HO at flare-up body region by plain radiograph) at Week 6. Change from Baseline in HO volume and new HO incidence were assessed by computed tomography (CT) at Week 12. Tissue edema was assessed by magnetic resonance imaging or ultrasound. Forty patients (7-53 years) were enrolled (placebo: N=10; palovarotene 5/2.5 mg: N=9; palovarotene 10/5 mg: N=21). Disease history was similar between groups. In the per-protocol population, the proportion of responders at Week 6 by plain radiograph was 100% with palovarotene 10/5 mg; 88.9% with palovarotene 5/2.5 mg; 88.9% with placebo (Cochran-Armitage trend test: p=0.17). At Week 12,...
Source: Cell Research - Category: Cytology Authors: Source Type: research