Takeaways From Terminated Phase III Trial on Roxadustat for MDS

A clinical trial of roxadustat for transfusion-dependent, lower-risk myelodysplastic syndromes (MDS) was terminated when its interim analysis outcomes did not meet statistical significance. This update was recently reported in the American Journal of Hematology.

“Despite MATTERHORN not meeting the primary endpoint, roxadustat was well tolerated, and many patients with transfusion-dependent, lower- or intermediate-risk MDS achieved [transfusion independence] with roxadustat treatment, especially those with the higher transfusion burden,” the trial investigators wrote.

MATTERHORN was a randomized, double-blind, phase III trial that enrolled 140 patients with very low- to intermediate-risk MDS and a transfusion burden of one to four packed red blood cell (pRBC) units every eight weeks. A total of 82 patients received thrice-weekly oral roxadustat 2.5 mg/kg and 58 received placebo.

The primary efficacy endpoint was transfusion independence for at least 56 days within 28 weeks of treatment. Final analysis found this outcome was achieved by 47.5% of patients who received roxadustat and 33.3% of those on placebo (P=.217).

A total of 36.1% of patients with a transfusion burden of at least two pRBC units every four weeks in the roxadustat arm achieved the primary endpoint, compared with 11.5% in the placebo arm (nominal P=.047).

There were four on-study mortalities in the roxadustat arm and three in the placebo arm, but none were attributed to treatment. Three patients who received roxadustat had progression to acute myeloid leukemia.

“The lack of a statistically significant treatment effect for roxadustat compared with placebo for the primary endpoint may be attributed to the inclusion of a higher percentage of patients in the placebo arm who did not or may not have eventually met transfusion-dependence criteria,” the investigators proposed.

Reference

Mittelman M, Henry DH, Glaspy JA, et al. Roxadustat versus placebo for patients with lower-risk myelodysplastic syndrome: MATTERHORN phase 3, double-blind, randomized controlled trial. Am J Hematol. 2024;99(9):1778-1789. doi:10.1002/ajh.27410