Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis

• DOI: 10.1001/jama.2023.5355
• Publication Date: 2023-05-09T17:50:04Z
• Authors: Toby M. Maher; Paul Ford; Kevin K. Brown; Ulrich Costabel; Vincent Cottin; Sonye K. Danoff; Irene Groenveld; Eric Helmer; R. Gisli Jenkins; Julie Milner; Geert Molenberghs; Bjorn Penninckx; Matthew J. Randall; Bernt Van Den Blink; Ann Fieuw; Charlotte Vandenrijn; Sanda Rocak; Ineke Seghers; Lixin Shao; Amit Taneja; Garrit Jentsch; Timothy R. Watkins; Wim A. Wuyts; Michael Kreuter; Nadia Verbruggen; Niyati Prasad; Marlies S. Wijsen...; ; Daniel Chambers; Michael Chia; Tamera Corte; Ian Glaspole; Nicole Goh; Mark Holmes; Monique Malouf; Francis Thien; Elizabeth Veitch; Benjamin Bondue; Caroline Dahlqvist; Antoine Froidure; Hans Slabbynck; Wim Wuyts; Claudia Cartagena...; Rosa Feijoó Seoane; Victor Martínez; Roxana Maturana; Juana Pavie Gallegos; Andres Rosenblut; Rafael Silva; Alvaro Undurraga ...; Martina Doubkova; Norbert Pauk; Martina Plackova; Martina Sterclova; Elisabeth Bendstrup; Saher B. Shaker; Ingrid Titlestad; Stephan Budweiser; Christian Grohé; Dirk Koschel; Michael Kreuter; Antje Prasse; Michael Weber; Hubert Wirtz; Katerina Antoniou; Zoe Daniil; Mina Gaga; Despoina Papakosta; Shinyu Izumi; Masaki Okamoto; Alfredo Guerreros...; Carlos Iberico Ba...; Alejandro Manuel ...; Aranzazu Campo Ez...; Jose Manuel Cifri...; Estrella Fernande...; Virginia Leiro; Maria Molina-Molina; Asunción Nieto Ba...; Jacobo Sellares T...; Claudia Valenzuela; Shih-Lung Cheng; Ping-Hung Kuo; Kang-Yun Lee; Chau-Chyun Sheu; Hakan Gunen; Nesrin Mogulkoc B...; Sibel Nayci; Huzaifa Adamali; Stephen Bianchi; Nazia Chaudhuri; Michael Gibbons; Simon Hart; Philip Molyneaux; Helen Parfrey; Gauri Saini; Lisa G Spencer; Sarah Wiscombe; Danielle Antin-Oz...; Rebecca Bascom; John Belperio; Edward Britt; John Fitzgerald; Diana Gomez Manja...; Mark Gotfried; Nishant Gupta; David Hotchkin; Mitchell Kaye; Mary Kreider; Shahrukh Kureishy; Peter Lacamera; Lisa Lancaster; Joseph Lasky; Daniel Lorch; Hannah Mannem; Lee Morrow; Teng Moua; Anoop Nambiar; Ganesh Raghu; Rishi Raj; Murali Ramaswamy; Raghu Reddy; Tonya Russell; Mary Beth Scholand; Barry Shea; Sally Suliman; Jeff Swigris; Krishna Thavarajah; Leslie Tolle; Rade Tomic; Neal Warshoff; Lewis Wesselius; Gordon Yung; Miguel Bergna; María De Salvo; Mariano Fernandez...; Alicia Rodriguez; Pablo Saez Scherb...; Deborah Assayag; Anil Dhar; Nasreen Khalil; Julie Morisset; Steeve Provencher; Chris Ryerson; Shane Shapera; Arnaud Bourdin; Bruno Crestani; Francois Lebargy; Martine Reynaud-G...; Francesco Tommaso...; Martin Claussen; Peter Hammerl; Christian Karagia...; Claus Keller; Winfried Randerath; Beate Stubbe; Eszter Csánky; Balazs Medgyasszay; Veronika Muller; Yochai Adir; Amir Bar-Shai; Neville Berkman; Gershon Fink; Mordechai Kramer; David Shitrit; Elena Bargagli; Stefano Gasparini; Sergio Harari; Claudia Ravaglia; Luca Richeldi; Carlo Vancheri; Masahito Ebina; Masaki Fujita; Kazuya Ichikado; Yoshikazu Inoue; Nobuhisa Ishikawa; Motoyasu Kato; Tetsuji Kawamura; Yasuhiro Kondoh; Yasuhiko Nishioka; Takashi Ogura; Isoko Owan; Takefumi Saito; Noriho Sakamoto; Koji Sakamoto; Masahiro Shirai; Takafumi Suda; Keisuke Tomii; Man Pyo Chung; Sung Hwan Jeong; Choon Sik Park; Jong Sun Park; Jin Woo Song; Soo-Taek Uh; Uriel Chavarria M...; Efrain Montano Go...; Alicia Ramirez; Moises Eduardo Se...; Paul Bresser; Henk Kramer; Remy Mostard; Esther Nossent; Marcel Veltkamp; Marlies Wijsenbeek; Lutz Beckert; Catherina L Chang; Andrew Veale; Margaret Wilsher; Michal Bednarek; Grzegorz Gasior; Grazyna Jasieniak...; Ewa Jassem; Robert Mroz; Wojciech Piotrowski; Ismail Abdullah; Anish Ambaram; Elvis Irusen; Michael Van der L...; Richard van Zyl-Smit; Paul Williams; James Allen; Francis Averill; Elizabeth Belloli; Anne Brown; Amy Case; Sachin Chaudhary; Gerard Criner; Kevin DeBoer; Daniel Dilling; Jeffrey Dorf; Richard Enelow; Neil Ettinger; Jeremy Feldman; Kevin Gibson; Jeffrey Golden; Mark Hamblin; Gary Hunninghake; Raj Karunakara; Hyun Kim; Tracy Luckhardt; Prema Menon; Lake Morrison; Justin Oldham; Nina Patel; Shelley Schmidt; Mary Strek; Ross Summer; Robert Sussman; James Tita; Srihari Veeraragh...; Timothy Whelan; Joseph Zibrak
• Keywords: Nintedanib; Pirfenidone; Vital capacity

There is a major need for effective, well-tolerated treatments idiopathic pulmonary fibrosis (IPF).To assess the efficacy and safety of autotaxin inhibitor ziritaxestat in patients with IPF.The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 2, were conducted Africa, Asia-Pacific region, Europe, Latin America, Middle East, North America (26 countries). A total 1306 IPF (525 at 106 sites 781 121 2). Enrollment began November 2018 both trials follow-up was completed early due to study termination on April 12, 2021, March 30, 2.Patients 1:1:1 receive 600 mg oral ziritaxestat, 200 or placebo once daily addition local standard care (pirfenidone, nintedanib, neither) least 52 weeks.The primary outcome annual rate decline forced vital capacity (FVC) week 52. The key secondary outcomes disease progression, time first respiratory-related hospitalization, change from baseline St George's Respiratory Questionnaire score (range, 0 100; higher scores indicate poorer health-related quality life).At termination, 525 (mean age: 70.0 [SD, 7.2] years 69.8 7.1] 2; male: 82.4% 81.2%, respectively). terminated after an independent data monitoring committee concluded that benefit risk profile no longer supported their continuation. Ziritaxestat did not improve FVC vs either study. In 1, least-squares mean -124.6 mL (95% CI, -178.0 -71.2 mL) -147.3 -199.8 -94.7 (between-group difference, 22.7 [95% -52.3 97.6 mL]), -173.9 -225.7 -122.2 difference placebo, -26.7 -100.5 47.1 mL]). -173.8 -209.2 -138.4 -176.6 -211.4 -141.8 2.8 -46.9 52.4 mL]) -174.9 -209.5 -140.2 1.7 -47.4 50.8 outcomes. all-cause mortality 8.0% 4.6% 6.3% placebo; it 9.3% 8.5% 4.7% placebo.Ziritaxestat compared receiving treatment pirfenidone nintedanib those treatment.ClinicalTrials.gov Identifiers: NCT03711162 NCT03733444.