TY - JOUR
T1 - Garetosmab in fibrodysplasia ossificans progressiva
T2 - a randomized, double-blind, placebo-controlled phase 2 trial
AU - Di Rocco, Maja
AU - Forleo-Neto, Eduardo
AU - Pignolo, Robert J.
AU - Keen, Richard
AU - Orcel, Philippe
AU - Funck-Brentano, Thomas
AU - Roux, Christian
AU - Kolta, Sami
AU - Madeo, Annalisa
AU - Bubbear, Judith S.
AU - Tabarkiewicz, Jacek
AU - Szczepanek, Małgorzata
AU - Bachiller-Corral, Javier
AU - Cheung, Angela M.
AU - Dahir, Kathryn M.
AU - Botman, Esmée
AU - Raijmakers, Pieter G.
AU - Mukaddam, Mona Al
AU - Tile, Lianne
AU - Portal-Celhay, Cynthia
AU - Sarkar, Neena
AU - Hou, Peijie
AU - Musser, Bret J.
AU - Boyapati, Anita
AU - Mohammadi, Kusha
AU - Mellis, Scott J.
AU - Rankin, Andrew J.
AU - Economides, Aris N.
AU - Trotter, Dinko Gonzalez
AU - Herman, Gary A.
AU - O’Meara, Sarah J.
AU - DelGizzi, Richard
AU - Weinreich, David M.
AU - Yancopoulos, George D.
AU - Eekhoff, E. Marelise W.
AU - Kaplan, Frederick S.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/10
Y1 - 2023/10
N2 - Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET–CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .
AB - Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET–CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .
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U2 - 10.1038/s41591-023-02561-8
DO - 10.1038/s41591-023-02561-8
M3 - Article
C2 - 37770652
AN - SCOPUS:85172773623
SN - 1078-8956
VL - 29
SP - 2615
EP - 2624
JO - Nature Medicine
JF - Nature Medicine
IS - 10
ER -