Use of thrombomodulin alfa (ART-123; Asahi Kasei Pharma Co; Tokyo, Japan) for the treatment of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is not recommended, according to phase 3 clinical trial results published in the American Journal of Respiratory and Critical Care Medicine.
AE-IPF is one of the leading causes of death in IPF, and coagulation abnormalities and endothelial damage have been considered part of the disease pathogenesis. ART-123 is a recombinant human soluble thrombomodulin that has anticoagulant and anti-inflammatory effects and has demonstrated an improvement in survival in patients with AE-IPF in small or retrospective clinical studies.
Researchers conducted a randomized double-blind placebo-controlled study (ClinicalTrials.gov Identifier: NCT02739165) at 27 sites in Japan in which 40 patients with AE-IFP received ART-123 and 37 patients received placebo. The researchers found that the survival proportion on day 90 was 72.5% in the ART-123 group and 89.2% in the placebo group (a difference of -16.7 percentage points, P =.0863). In the safety population, bleeding adverse events occurred in 23.8% of the ART-123 group and in 10.5% of the placebo group, which was expected due to the mechanism of action of ART-123.
The researchers noted that baseline imbalances could have potentially account the unexpected study results. In addition, the survival proportion on day 90 was even higher than assumed due to the improvement of the standard of care level and the fact that patients were in a clinical study setting. This may have reduced the power of the study, making it difficult to discern the drug’s effect on mortality.
“In conclusion, ART-123 did not improve the 90-day survival proportion in patients with AE-IPF,” the authors wrote. Therefore, ART-123 for the treatment of AE-IFP is not recommended.
Disclosure: This clinical trial was supported by Asahi-Kasei Pharma Corporation. Please see the original reference for a full list of authors’ disclosures.
Kondoh Y, Azuma A, Inoue Y, et al. Thrombomodulin alfa for acute exacerbation of idiopathic pulmonary fibrosis: a randomized, double-blind, placebo-controlled trial [published on January 9, 2020]. Am J Respir Crit Care Med. doi:10.1164/rccm.201909-1818OC