Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial Maja Di Rocco 1, Eduardo Forleo-Neto 2, Robert J Pignolo 3, Richard Keen 4, Philippe Orcel 5 6, Thomas Funck-Brentano 5 6, Christian Roux 7, Sami Kolta 7, Annalisa Madeo 1, Judith S Bubbear 4, Jacek Tabarkiewicz 8, Małgorzata Szczepanek 8, Javier Bachiller-Corral 9, Angela M Cheung 10, Kathryn M Dahir 11, Esmée Botman 12, Pieter G Raijmakers 13, Mona Al Mukaddam 14, Lianne Tile 10, Cynthia Portal-Celhay 2, Neena Sarkar 2, Peijie Hou 2, Bret J Musser 2, Anita Boyapati 2, Kusha Mohammadi 2, Scott J Mellis 15, Andrew J Rankin 2, Aris N Economides 2, Dinko Gonzalez Trotter 2, Gary A Herman 2, Sarah J O'Meara 2, Richard DelGizzi 2, David M Weinreich 2, George D Yancopoulos 2, E Marelise W Eekhoff # 12, Frederick S Kaplan

Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial Maja Di Rocco 1, Eduardo Forleo-Neto 2, Robert J Pignolo 3, Richard Keen 4, Philippe Orcel 5 6, Thomas Funck-Brentano 5 6, Christian Roux 7, Sami Kolta 7, Annalisa Madeo 1, Judith S Bubbear 4, Jacek Tabarkiewicz 8, Małgorzata Szczepanek 8, Javier Bachiller-Corral 9, Angela M Cheung 10, Kathryn M Dahir 11, Esmée Botman 12, Pieter G Raijmakers 13, Mona Al Mukaddam 14, Lianne Tile 10, Cynthia Portal-Celhay 2, Neena Sarkar 2, Peijie Hou 2, Bret J Musser 2, Anita Boyapati 2, Kusha Mohammadi 2, Scott J Mellis 15, Andrew J Rankin 2, Aris N Economides 2, Dinko Gonzalez Trotter 2, Gary A Herman 2, Sarah J O'Meara 2, Richard DelGizzi 2, David M Weinreich 2, George D Yancopoulos 2, E Marelise W Eekhoff # 12, Frederick S Kaplan https://pubmed.ncbi.nlm.nih.gov/37770652/ FDA Approves Third Treatment for Fibrodysplasia Ossificans Progressiva Action The U.S. Food and Drug Administration (FDA) has approved Atebrioz (zilurgisertib) tablets to reduce the volume of total new heterotopic ossification (bone formation outside the skeleton) in adults and pediatric patients 12 years and older with fibrodysplasia ossificans progressiva (FOP). The recommended starting dosage is 100 mg orally once daily with or without food. Disease or Condition Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by a mutation in activin A receptor-type 1, which controls new bone growth. As a result, connective tissues such as muscle, tendons, and ligaments gradually turn into bone, causing limited movement, deformities, severe disability, and early death. Effectiveness The effectiveness of Atebrioz was evaluated in a randomized, double-blind, placebo controlled trial (NCT05090891) in which 63 patients with FOP were randomly assigned to receive Atebrioz 100 mg or placebo once daily for 24 weeks followed by a 292-week, single-arm, open-label extension period during which patients received Atebrioz 100 mg daily. Atebrioz’s efficacy was based on the change from baseline in volume of total new heterotopic ossification compared to placebo during the double blind period, assessed by whole body CT scans. At Week 24, the group of patients receiving Atebrioz had an average 3.2 cm³ decrease in volume of total new heterotopic ossification, whereas the placebo group had a 24.6 cm³ increase. Safety Information Atebrioz can cause fetal harm based on data from animal studies. Patients of reproductive potential should use effective contraception and should immediately discontinue Atebrioz and contact their healthcare provider if pregnancy occurs. The most common side effects are headache, joint pain, upper respiratory tract infection, nosebleeds, and nausea. Atebrioz should not be taken with certain other medications, as described in the label. Designations Atebrioz received fast track, priority review and orphan drug designation for this indication.