PT  - JOURNAL ARTICLE
AU  - Toby M. Maher
AU  - Ulrich Costabel
AU  - Marilyn K. Glassberg
AU  - Yasuhiro Kondoh
AU  - Takashi Ogura
AU  - Mary Beth Scholand
AU  - David Kardatzke
AU  - Monet Howard
AU  - Julie Olsson
AU  - Margaret Neighbors
AU  - Paula Belloni
AU  - Jeffrey J. Swigris
TI  - Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis
AID  - 10.1183/13993003.02442-2019
DP  - 2020 Jan 01
TA  - European Respiratory Journal
PG  - 1902442
4099  - http://erj.ersjournals.com/content/early/2020/08/13/13993003.02442-2019.short
4100  - http://erj.ersjournals.com/content/early/2020/08/13/13993003.02442-2019.full
AB  - This phase 2, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of lebrikizumab, an interleukin-13 monoclonal antibody, alone or with background pirfenidone therapy, in patients with idiopathic pulmonary fibrosis (IPF).Patients with IPF aged ≥40 years with % predicted forced vital capacity (%FVC) 40%–100% and diffusing capacity for carbon monoxide 25%–90% and who were treatment-naive (Cohort A) or receiving pirfenidone (2403 mg·day−1; Cohort B) were randomised 1:1 to receive lebrikizumab 250 mg or placebo subcutaneously every 4 weeks. The primary endpoint was annualised rate of %FVC decline over 52 weeks.In Cohort A, 154 patients were randomised to receive lebrikizumab (n=78) or placebo (n=76). In Cohort B, 351 patients receiving pirfenidone were randomised to receive lebrikizumab (n=174) or placebo (n=177). Baseline demographics were balanced across treatment arms in both cohorts. The primary endpoint (annualised rate of %FVC decline) was not met in Cohort A (lebrikizumab versus placebo, −5.2% versus −6.2%; p=0.456) or Cohort B (lebrikizumab versus placebo, −5.5% versus −6.0%; p=0.557). In Cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio, 0.42 [95% CI, 0.17–1.04]). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.Lebrikizumab alone or with pirfenidone was not associated with reduced %FVC decline over 52 weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Maher reports grants from Funding from GlaxoSmithKline and University of California, Berkeley (UCB), during the conduct of the study; and Served as a consultant and speaker for Apellis, AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Indalo, Novartis, Pliant, ProMetic, Respivnat, Roche, Samumed and UCB.Conflict of interest: Dr. Costabel reports was a member of a study adjudication committee for Gilead; has served as a consultant and speaker for Bayer, Boehringer Ingelheim and InterMune/Roche; has received grants from Boehringer Ingelheim and InterMune and has served as a consultant for Centocor, Fibrogen, Gilead, GlaxoSmithKline, UCB Celltech and Biogen.Conflict of interest: Dr. Glassberg reports grants from Genentech/Roche, during the conduct of the study; and was a member of the ASCEND study steering committee; has served as a consultant for Bellerophon, Boehringer Ingelheim, Bristol Myers Squibb, InterMune, RedX Pharma and Roche.Conflict of interest: Dr. Kondoh reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; and has served as a consultant for Genentech and has served as a consultant and speaker for Asahi Kasei, Boehringer Ingelheim, Eisai, Janssen, Kyorin, Mitsubishi Tanabe Pharma, Novartis and Shionogi.Conflict of interest: Dr. Ogura reports grants from Boehering Ingelheim and the Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; and has served as a consultant or speaker for Asahi Kasei, Boehringer Ingelheim, Eisai, Nitto Denko, Shionogi and Toray.Conflict of interest: Dr. Scholand has served on advisory boards for Boehringer Ingelheim and InterMune/Roche/Genentech.Conflict of interest: Dr. Kardatzke is an employee of Genentech, Inc.Conflict of interest: Dr. Howard is an employee of Genentech, Inc.Conflict of interest: Dr. Olsson is an employee of Genentech, Inc.Conflict of interest: Dr. Neighbors is an employee of Genentech, Inc.Conflict of interest: Dr. Belloni is an employee of Genentech, Inc.Conflict of interest: Dr. Swigris reports grants from InterMune, personal fees from Genentech, during the conduct of the study; and was a member of the ASCEND study steering committee, served on a scientific advisory board for InterMune, and served as a consultant to Boehringer Ingelheim and Roche.