Ziritaxestat not found effective in patients with idiopathic pulmonary fibrosis: JAMA

A new study by Toby Maher and team showed that patients with idiopathic pulmonary fibrosis (IPF) getting standard of care medication with pirfenidone or nintedanib or those not receiving standard of care treatment did not experience any differences in clinical outcomes between ziritaxestat and placebo. The findings of this study were published in the Journal of American Medical Association.

The 26 nations that made up the continents of Africa, Asia-Pacific, Europe, Latin America, the Middle East, and North America participated in the phase 3 randomized clinical trials known as ISABELA 1 and ISABELA 2. 1306 IPF patients in total were randomly assigned. Both trials saw the start of enrollment in November 2018, and follow-up was finished early owing to study terminations for ISABELA 1 and ISABELA 2 on April 12, 2021, and March 30, 2021, respectively. In addition to the regional standard of therapy (pirfenidone, nintedanib, or neither), patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or a placebo once daily for at least 52 weeks.

The key findings of this study were;

1. 525 patients were randomly assigned to ISABELA 1 and 781 patients to ISABELA 2 at the time the trial was terminated.

2. An independent data and safety monitoring committee decided that the benefit to risk profile of ziritaxestat no longer supported the continuation of the studies, hence they were stopped early.

3. In either research, ziritaxestat did not enhance the yearly rate of FVC decrease in comparison to placebo.

4. With 600 mg of ziritaxestat compared to -147.3 mL with placebo, and -173.9 mL with 200 mg of ziritaxestat, the least-squares mean annual rate of FVC reduction in ISABELA 1 was -124.6 mL.

5. With 600 mg of ziritaxestat, the least-squares mean annual rate of FVC reduction in ISABELA 2 was -173.8 mL, compared to -176.6 mL with placebo and -174.9 mL with 200 mg of ziritaxestat.

6. For the important secondary outcomes, there was no advantage of ziritaxestat compared to placebo.

7. In ISABELA 1, all-cause mortality was 8.0% when ziritaxestat 600 mg was used, 4.6% when ziritaxestat 200 mg was used, and 6.3% when a placebo was used; in ISABELA 2, it was 9.3% when ziritaxestat 600 mg was used, 8.5% when ziritaxestat 200 mg was used, and 4.7% when a placebo was used.

In patients with IPF getting standard of care medication with pirfenidone or nintedanib or those not receiving standard of care treatment, ziritaxestat did not enhance clinical outcomes compared to placebo.

Reference:

Maher, T. M., Ford, P., Brown, K. K., Costabel, U., Cottin, V., Danoff, S. K., Groenveld, I., Helmer, E., Jenkins, R. G., Milner, J., Molenberghs, G., Penninckx, B., Randall, M. J., Van Den Blink, B., Fieuw, A., Vandenrijn, C., Rocak, S., Seghers, I., … Shao, L. (2023). Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis. In JAMA (Vol. 329, Issue 18, p. 1567). American Medical Association (AMA). https://doi.org/10.1001/jama.2023.5355