학술논문
Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial
Document Type
Original Paper
Author
Di Rocco, Maja; Forleo-Neto, Eduardo; Pignolo, Robert J.; Keen, Richard; Orcel, Philippe; Funck-Brentano, Thomas; Roux, Christian; Kolta, Sami; Madeo, Annalisa; Bubbear, Judith S.; Tabarkiewicz, Jacek; Szczepanek, Małgorzata; Bachiller-Corral, Javier; Cheung, Angela M.; Dahir, Kathryn M.; Botman, Esmée; Raijmakers, Pieter G.; Al Mukaddam, Mona; Tile, Lianne; Portal-Celhay, Cynthia; Sarkar, Neena; Hou, Peijie; Musser, Bret J.; Boyapati, Anita; Mohammadi, Kusha; Mellis, Scott J.; Rankin, Andrew J.; Economides, Aris N.; Trotter, Dinko Gonzalez; Herman, Gary A.; O’Meara, Sarah J.; DelGizzi, Richard; Weinreich, David M.; Yancopoulos, George D.; Eekhoff, E. Marelise W.; Kaplan, Frederick S.
Source
Nature Medicine. 29(10):2615-2624
Subject
Language
English
ISSN
1078-8956
1546-170X
1546-170X
Abstract
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.
In the LUMINA-1 trial for fibrodysplasia ossificans progressiva, garetosmab, an activin A monoclonal antibody, did not lead to significant changes in heterotopic ossification lesion activity in pre-existing lesions in period 1. Garetosmab prevented the formation of new lesions in both periods 1 and 2.
In the LUMINA-1 trial for fibrodysplasia ossificans progressiva, garetosmab, an activin A monoclonal antibody, did not lead to significant changes in heterotopic ossification lesion activity in pre-existing lesions in period 1. Garetosmab prevented the formation of new lesions in both periods 1 and 2.